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Aberrant glycosylation is a key mechanism employed by cancer cells to evade immune surveillance, induce angiogenesis and metastasis, among other hallmarks of cancer. Sialic acids, distinctive terminal glycan structures located on glycoproteins or glycolipids, are prominently upregulated across various tumor types, including colorectal cancer (CRC). Sialylated glycans modulate anti-tumor immune responses through their interactions with Siglecs, a family of glycan-binding receptors with specificity for sialic acid-containing glycoconjugates, often resulting in immunosuppression. In this paper, we investigated the immunomodulatory function of ST3Gal5, a sialyltransferase that catalyzes the addition of α2-3 sialic acids to glycosphingolipids, since lower expression of ST3Gal5 is associated with better survival of CRC patients. We employed CRISPR/Cas9 to knock out the ST3Gal5 gene in two murine CRC cell lines MC38 and CT26. Glycomics analysis confirmed the removal of sialic acids on glycolipids, with no discernible impact on glycoprotein sialylation. Although knocking out ST3Gal5 in both cell lines did not affect in vivo tumor growth, we observed enhanced levels of regulatory T cells in CT26 tumors lacking ST3Gal5. Moreover, we demonstrate that the absence of ST3Gal5 affected size and blood vessel density only in MC38 tumors. In summary, we ascertain that sialylation of glycosphingolipids has a limited influence on the anti-tumor immune response in CRC, despite detecting alterations in the tumor microenvironment, possibly due to a shift in ganglioside abundance. [ABSTRACT FROM AUTHOR]

The article offers information on the challenges and advancements in hematopoietic stem cell transplantation (HCT) over the past 50 years, as chronicled through key papers in the JCI. Topics include the curative potential of HCT for various hematologic diseases, the challenges of allogeneic HCT such as relapse and graft-versus-host disease (GVHD), and the immunologic complexities underlying these challenges.

Background: HBV-specific T lymphocytes are pivotal in eliminating the hepatitis B virus (HBV) and regulating intrahepatic inflammatory reactions. Effective T cell responses curtail HBV infection; however, compromised immunity can result in persistent infection. Beyond the acute phase, the continued presence of antigens and inflammation leads to the increased expression of various inhibitory receptors, such as PD-1, CTLA-4, Tim-3, LAG3, 2B4, CD160, BTLA, and TIGIT. This escalates the dysfunction of and diminishes the immune and proliferative abilities of T cells. Methods: In this study, we reviewed English-language literature from PubMed, Web of Science, and Scopus up to 9 July 2023. This paper aims to elucidate the inhibitory effects of these receptors on HBV-specific T lymphocytes and how immune function can be rejuvenated by obstructing the inhibitory receptor signaling pathway in chronic HBV patients. We also summarize the latest insights into related anti-HBV immunotherapy. Result: From 66 reviewed reports, we deduced that immunotherapy targeting inhibitory receptors on T cells is a reliable method to rejuvenate T cell immune responses in chronic HBV patients. However, comprehensive combination therapy strategies are essential for a functional cure. Conclusions: Targeting T cell suppressor receptors and combining immunotherapy with antiviral treatments may offer a promising approach towards achieving a functional cure, urging future research to prioritize effective combination therapeutic strategies for chronic HBV infection. [ABSTRACT FROM AUTHOR]

Background: In the global effort to discover biomarkers for cancer prognosis, prediction tools have become essential resources. TCR (T cell receptor) repertoires contain important features that differentiate healthy controls from cancer patients or differentiate outcomes for patients being treated with different drugs. Considering, tools that can easily and quickly generate and identify important features out of TCR repertoire data and build accurate classifiers to predict future outcomes are essential. Results: This paper introduces GENTLE (GENerator of T cell receptor repertoire features for machine LEarning): an open-source, user-friendly web-application tool that allows TCR repertoire researchers to discover important features; to create classifier models and evaluate them with metrics; and to quickly generate visualizations for data interpretations. We performed a case study with repertoires of TRegs (regulatory T cells) and TConvs (conventional T cells) from healthy controls versus patients with breast cancer. We showed that diversity features were able to distinguish between the groups. Moreover, the classifiers built with these features could correctly classify samples ('Healthy' or 'Breast Cancer')from the TRegs repertoire when trained with the TConvs repertoire, and from the TConvs repertoire when trained with the TRegs repertoire. Conclusion: The paper walks through installing and using GENTLE and presents a case study and results to demonstrate the application's utility. GENTLE is geared towards any researcher working with TCR repertoire data and aims to discover predictive features from these data and build accurate classifiers. GENTLE is available on https://github.com/dhiego22/gentle and https://share.streamlit.io/dhiego22/gentle/main/gentle.py. [ABSTRACT FROM AUTHOR]

In the first paper [[10]], the epidemiologic, clinical, and immunological features of CVID-associated giardiasis are reviewed, evidencing that patients with giardiasis more commonly have reduced IgA levels and lower levels of switched memory B cells. 35566429 12 Pieniawska-'Smiech K., Kuraszewicz A., Sado J., 'Smiech K., Lewandowicz-Uszy'nska A. Assessment of COVID-19 Incidence and the Ability to Synthesise Anti-SARS-CoV-2 Antibodies of Paediatric Patients with Primary Immunodeficiency. The atypical presentation of IEI is also the main focus of the paper by Morawska et al., which explores the spectrum of atopic manifestations in patients with selective IgA deficiency (sIgAD). This work analyzes the most common autoimmune manifestations in patients with antibody deficiencies, combined immunodeficiencies, and immune dysregulation disorders, and also introduces some specific monogenic entities that are used as a paradigm of "druggable" IEI. [Extracted from the article]

Summary: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia. This bibliometric analysis was applied to identify the characteristics of global scientific output, the hotspots, and frontiers of ITP over the past 10 years. We retrieved publications from 2011 to 2021 from the Web of Science Core Collection (WoSCC). Bibliometrix package, VOSviewer, and Citespace were used to analyse and visualize the trend, distribution, and hotspots of research on ITP. Altogether, there were 2084 papers, written by 9080 authors from 410 organizations in 70 countries/regions, published in 456 journals with 37 160 co‐cited references. In the last decades, the most productive journal was British Journal of Haematology, China was the most productive country. and the most cited journal was Blood. Shandong University was the most productive institution in the field of ITP. NEUNERT C, 2011, BLOOD, CHENG G, 2011, LANCET, and PATEL VL, 2012, BLOOD were the top three most cited documents. "Thrombopoietin receptor agonist", "regulatory T cell" and "sialic acid" were three hotspots of the last decade. And "immature platelet fraction", "Th17", and "fostamatinib" would be research frontiers in the feature. The present study provided a novel insight for future research directions and scientific decision‐making. [ABSTRACT FROM AUTHOR]

Allergen-immunotherapy (AIT) is an efficacious and disease-modifying treatment option for IgE-mediated diseases. Among these allergic rhinitis, insect venom allergy, food allergy, and allergic asthma are the most common candidates for AIT. AIT gives rise to clinical immunotolerance which may last for years after the treatment cessation. Mechanisms of AIT include suppression of allergic inflammation in target tissues and stimulation of the production of blocking antibodies, especially IgG4 and IgA. These mechanisms are followed by a reduction of underlying allergen-specific Th2 cell-driven responses to the allergens. Tolerance induction takes place through the desensitization of effector cells and stimulation of regulatory T cells that show their effects by mechanisms involving cell-cell cross-talk, but also other mechanisms, e.g., by the production of immunomodulatory cytokines such as, e.g., IL-10 and TGF-beta. From a personalized medical perspective, there is a need for clinical biomarkers of value in selecting responders and optimizing patient care during AIT. Also, a deeper understanding of underlying mechanistic processes will improve AIT's future outcomes. In this paper, the current knowledge of mechanisms in AIT is reviewed with a special focus on biomarkers of this therapy. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a global health problem with increasing prevalence and association with an enormous medical and socioeconomic burden. New recognition of immune cells such as type 2 innate lymphocytes (ILC2s), T helper (Th2) 2 cells, follicular helper T cells, follicular regulatory T cells, regulatory T cells, B cells, dendritic cells, and epithelial cells in AR pathogenesis has been updated in this review paper. An in‐depth understanding of the mechanisms underlying AR will aid the identification of biomarkers associated with disease and ultimately provide valuable parameters critical to guide personalized targeted therapy. As the only etiological treatment option for AR, allergen‐specific immunotherapy (AIT) has attracted increasing attention, with evidence for effectiveness of AIT recently demonstrated in several randomized controlled trials and long‐term real‐life studies. The exploration of biologics as therapeutic options has only involved anti‐IgE and anti‐type 2 inflammatory agents; however, the cost‐effectiveness of these agents remains to be elucidated precisely. In the midst of the currently on‐going COVID‐19 pandemic, a global life‐threatening disease, although some studies have indicated that AR is not a risk factor for severity and mortality of COVID‐19, this needs to be confirmed in multi‐centre, real‐life studies of AR patients from different parts of the world. [ABSTRACT FROM AUTHOR]

Tumor cells express a high quantity of exosomes packaged with unique cargos under hypoxia, an important characteristic feature in solid tumors. These hypoxic tumor-derived exosomes are, crucially, involved in the interaction of cancer cells with their microenvironment, facilitating not only immune evasion, but increased cell growth and survival, enhanced angiogenesis, epithelial–mesenchymal transition (EMT), therapeutic resistance, autophagy, pre-metastasis, and metastasis. This paper explores the tumor microenvironment (TME) remodeling effects of hypoxic tumor-derived exosome towards facilitating the tumor progression process, particularly, the modulatory role of these factors on tumor cell immune evasion through suppression of immune cells, expression of surface recognition molecules, and secretion of antitumor soluble factor. Tumor-expressed exosomes educate immune effector cells, including macrophages, monocytes, T cells, natural killer (NK) cells, dendritic cells (DCs), γδ T lymphocytes, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mast cells, and B cells, within the hypoxic TME through the release of factors that regulate their recruitment, phenotype, and function. Thus, both hypoxia and tumor-derived exosomes modulate immune cells, growth factors, cytokines, receptor molecules, and other soluble factors, which, together, collaborate to form the immune-suppressive milieu of the tumor environment. Exploring the contribution of exosomal cargos, such as RNAs and proteins, as indispensable players in the cross-talk within the hypoxic tumor microenvironmental provides a potential target for antitumor immunity or subverting immune evasion and enhancing tumor therapies. [ABSTRACT FROM AUTHOR]

• FOXP3 controls Treg differentiation and activity. • FOXP3 induces metabolic versatility in intra-tumoral Tregs. • Treg subsets show different reliance on FOXP3. Dysregulation of regulatory T cells (Tregs) is described in the context of inflammatory and autoimmune diseases, and cancer. Forkhead box P3 (FOXP3) is a transcription factor that its activity is an indicator of Treg identity. FOXP3 induces metabolic versatility in intra-tumoral Tregs, so that its deficiency mediates Treg instability or even gives rise to the acquisition of effector T cell phenotype. FOXP3 dysregulation and defectiveness occurs upon ubiquitination, methylation and presumably acetylation. Stimulators of PTEN, mammalian target of rapamycin complex 2 (mTORC2), and nucleus accumbens–associated protein-1 (NAC1), and inhibitors of B lymphocyte-induced maturation protein-1 (Blimp-1), Deltex1 (DTX1) and ubiquitin-specific peptidase 22 (USP22) are suggested to hamper FOXP3 stability, and to promote its downregulation and further Treg depletion. A point is that Treg subsets reveal different reliance on FOXP3, which indicates that not all Tregs are strictly dependent on FOXP3, and presumably Tregs with different origin rely on diverse regulators of FOXP3 stability. The focus of this review is over the current understanding toward FOXP3, its activity in Tregs and influence from different regulators within tumor microenvironment (TME). Implication of FOXP3 targeting in cancer immunotherapy is another focus of this paper. [ABSTRACT FROM AUTHOR]

Summary: The immune system plays a critical role in protecting the host against infection but is subject to numerous levels of control that are necessary to prevent pathological, tissue-damaging responses. Inappropriate inflammatory immune responses to self-antigens, innocuous commensal microorganisms, or environmental antigens can lead to chronic, debilitating, and degenerative diseases. Regulatory T cells have an essential, non-redundant, and dominant function in preventing pathological immune responses, as shown by the development of systemic fatal autoimmunity in humans and animals with a genetic deficiency in regulatory T cells. In addition to controlling immune responses, there is a growing understanding that regulatory T cells also contribute directly to tissue homeostasis by promoting tissue regeneration and repair. For these reasons, the prospect of enhancing regulatory T-cell numbers and/or function in patients represents an appealing therapeutic opportunity with potential applications in many diseases, including some where the pathological role of the immune system has only recently been recognized. Approaches to enhance regulatory T cells are now starting to be explored in clinical studies in humans. This review series brings together papers highlighting the Treg-enhancing approaches that are most advanced clinically and examples of therapeutic opportunities based on our growing understanding of regulatory T-cell functions. [ABSTRACT FROM AUTHOR]

Background: At present, patients with myocardial infarction remain an increased risk for myocardial ischemia/reperfusion injury (MI/RI). There lacks effectively method to treat MI/RI in clinic. For the treatment of MI/RI, it is still a bottleneck to effectively deliver drug to ischemic myocardium. In this paper, a regulatory T cells (Tregs) biomimetic nanoparticle (CsA@PPTK) was prepared by camouflaging nanoparticle with platelet membrane. Results: CsA@PPTK actively accumulated in ischemic myocardium of MI/RI mice. CsA@PPTK significantly scavenged reactive oxygen species (ROS) and increased the generation of Tregs and the ratio of M2 type macrophage to M1 type macrophage in ischemic myocardium. Moreover, CsA@PPTK significantly attenuated apoptosis of cardiomyocytes and reduced the infarct size and fibrosis area in ischemic myocardium. CsA@PPTK markedly decreased the protein expression of MMP-9 and increased the protein expression of CX43 in ischemic myocardium tissue. Subsequently, the remodeling of the left ventricle was significant alleviated, and heart function of MI/RI mice was markedly improved. Conclusion: CsA@PPTK showed significant therapeutic effect on MI/RI, and it has great potential application in the treatment of MI/RI. [ABSTRACT FROM AUTHOR]

Background: Clinical studies have shown that the efficacy of programmed cell death receptor-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors on glioblastoma (GBM) is much lower than what is expected because of the low immunogenicity of GBM. Ferroptosis of cancer cells can induce the maturation of dendritic cells (DC cells) and increase the activity of T cell. The activated T cells release IFN-γ, which subsequently induces the ferroptosis of cancer cells. Thus, the aim of this paper is to set up a new GBM-targeted drug delivery system (Fe3O4-siPD-L1@M-BV2) to boost ferroptosis for immunotherapy of drug-resistant GBM. Results: Fe3O4-siPD-L1@M-BV2 significantly increased the accumulation of siPD-L1 and Fe2+ in orthotopic drug-resistant GBM tissue in mice. Fe3O4-siPD-L1@M-BV2 markedly decreased the protein expression of PD-L1 and increased the ratio between effector T cells and regulatory T cells in orthotopic drug-resistant GBM tissue. Moreover, Fe3O4-siPD-L1@M-BV2 induced ferroptosis of GBM cells and maturation of DC cell, and it also increased the ratio between M1-type microglia and M2-type microglia in orthotopic drug-resistant GBM tissue. Finally, the growth of orthotopic drug-resistant GBM in mice was significantly inhibited by Fe3O4-siPD-L1@M-BV2. Conclusion: The mutual cascade amplification effect between ferroptosis and immune reactivation induced by Fe3O4-siPD-L1@M-BV2 significantly inhibited the growth of orthotopic drug-resistant GBM and prolonged the survival time of orthotopic drug-resistant GBM mice. [ABSTRACT FROM AUTHOR]

Previously, we prepared a chondroitin sulfate-soluble undenatured type II collagen complex (CS-SC II) with low salt content. This paper further explored the differences between CS-SC II and SC II in terms of gastrointestinal digestive characteristics and osteoarthritis (OA) improvement. In vitro and in vivo experiments showed that the gastric digestive stability of CS-SC II was high under both pH 2.0 and pH 3.0, the α1 chain and triple helix structure of type II collagen retained >60 %. However, SC II had high gastric digestive stability only under pH 3.0. Furthermore, intestinal digestion had little effect on α1 chains of CS-SC II and SC II, and distribution experiments showed that they might exert their biological activities in the intestine. CS-SC II had obvious improvement in OA rats at 1.0 mg/kg/d, that is, the joint swelling was significantly reduced and the weight-bearing ratio of the right hind limb was increased to 49 %, which was close to that of 4.0 mg/kg/d SC II. The wear of articular cartilage, Mankin and OARSI scores of rats in CS-SC II group were significantly reduced. The effects of low-dose CS-SC II on the proportion of regulatory T cells (Treg), mRNA expression of OA key biomarkers (Il6, Ccl7, MMP-3 and MMP13) and signaling pathway genes (NF-κB, AKT or AMPKα) were comparable to those of high-dose SC II. These results showed that CS-SC II might have greater potential to improve OA at a lower dose than SC II due to its high gastrointestinal digestive stability at a wide range of pH conditions. [Display omitted] • Study on chondroitin sulfate-soluble undenatured type II collagen complex (CS-SC II) • The gastric digestive stability of CS-SC II was high under both pH 2.0 and pH 3.0. • SC II had high gastric digestive stability only under pH 3.0. • The improvement of 1.0 mg/kg/d CS-SC II in OA rats was close to 4.0 mg/kg/d SC II. • CS-SC II regulated the expression of key OA biomarkers and signaling pathway genes. [ABSTRACT FROM AUTHOR]

Polyphenols are a big family of phytochemicals that includes a wide range of natural substances with various biological activities. Amongst these activities, the immunomodulatory property has significant importance due to the central and vital roles of the immune system in the human body. The biological activities of polyphenols depend crucially on the chemical structure and the biotransformation undergone in the body. The glycosylation state of polyphenols and its diversity have a significant impact on the immunomodulatory activity, while there is a lack of a comprehensive review paper in this concept. Hence, we aimed to review the body of literature to light the way for effective modulation of the immune system function using dietary polyphenols. However, due to the significant diversity in the structure and biotransformation of polyphenols, it is hard to draw a general pattern in this regard. The sugar moiety, type, position, and extent of glycosylation determine the antioxidant, anti-inflammatory, and generally the immunomodulatory activities of polyphenols. In conclusion, this study provides a new comparative approach regarding the immunomodulatory activities of polyphenols versus their metabolites. Moreover, we conclude that polyphenols can modulate the immune system, while each polyphenol has its structural relevance and should be assessed case by case. Abbreviations: BBC: brush border cell; GI: gastrointestinal tract; LPH: lactase-phlorizin hydrolase; CBG: cytosolic beta-glucosidase; CYP: cytochrome p450 enzymes; COMT: catechol-O-methyltransferases; SULT: sulphotransferases; UDPGT: uridine-5′-diphosphate glucuronosyl-transferases; ABC: ATP-binding cassette; ET: transporters, ellagitannin; EA: ellagic acid; EGCG: epigallocatechin-3- gallate; DC: dendritic cell; Th: T helper; NK: natural killer; Treg: cells, regulatory T cells; TGFβ: transforming growth factor β; Foxp3: forkhead box P3; T-bet: T-box transcription factor; RORγt: Retineic-acid-receptor-related orphan nuclear receptor gamma; STAT: Signal transducer and activator of transcription; AhR: aryl hydrocarbon receptor; XRE: xenobiotic-responsive elements; PWM: pokeweed mitogen; Igs: immunoglobulins; PGE2: prostaglandin E2; TNF-α: tumor necrosis factor α; COX-2: cyclooxygenase-2; iNOS: inducible nitric oxide synthase; LPS: lipopolysaccharide; ApoE: apolipoprotein E; NF-κB: nuclear factor kappa light chain enhancer of activated B cells; JNK: c-Jun N-terminal kinases; IκBα: IκB alpha; IKK: IκB kinase; hsCRP: high sensitivity C reactive protein; ICAM-1: Intracellular adhesion molecule-1; MCP-1: Monocyte chemoattractant protein-1; VCAM-1: vascular cellular adhesion molecule-1; M3Gal: myricetin 3-O-β-D-galactopyranoside; Q3Glc: quercetin 3-O-β-D-glucopyranoside; Q3Rut: quercetin 3-O-β-D-rutinoside; and Q3Gal: quercetin 3-O-β-D-galactopyranoside; ISR, 3-methyl metabolite of quercetin: isorhamnetin; TAM, 4ʹ-O-methyl quercetin: tamarixetin; ConA: Concanavalin A; ROS: Reactive oxygen species; ROS: Reactive oxygen species; THC: tetrahydrocurcumin; DHC: dihydrocurcumin; OHC: octahydrocurcumin; HHC: hexahydrocurcumin; NaC: sodium curcuminate; TEC: triethyl curcumin; DAC: diacetyl curcumin; HHC: hexahydrocurcumin; PLA2: phospholipase A2; TDM: trimethoxydibenzoylmethane; DBM: dibenzoylmethane; cPLA2: cytosolic phospholipase A2; 5-LOX: 5-lipoxygenase; IC50: half maximal inhibitory concentration; PI3K: phosphatidylinositol-3-Kinase; 12-HHT: 12(S)-hydroxy(5Z,8E,10E)-heptadecatrienoic acid; TXB2: thromboxane B2; 12-HETE: 12(S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoic acid; MIP-1a: macrophage inflammatory protein-1a; DHG: dihydrogenistein; DHD: dihydrodaidzein; O-DMA: O-desmethylangolensin; MnSOD: manganese superoxide dismutase; DP: degree of polymerization; MMPs: matrix metalloproteinases; EC: epicatechin; EGC: epigallocatechin; C3G: cyanidin-3-glucoside; MAPK: mitogen-activated protein kinase; PI3K/PKB: phosphoinositide-3-kinase/protein kinase B; PA: protocatechuic acid; BR: black rice; HHDP: hexahydroxydiphenoyl; AP-1: activator protein 1; TSP: thrombospondin; eNOS: endothelial-nitric oxide synthase; Nrf2: nuclear factor erythroid 2–related factor 2; PAI-1: plasminogen activator inhibitor-1; C–C motif: chemokine; CCL2: ligand 2; miR-155: microRNA-155; M-CSF: macrophage colony-stimulating factor; BMDM: bone marrow-derived macrophage; ORAC: oxygen radical absorbance capacity; PCL: photochemiluminescence; FRAP: ferric reducing antioxidant power; ABTS: 2,2ʹ-azinobis (3-ethylbenzothiazoline-6-sulfonic acid); TEAC: trolox equivalent antioxidant capacity; DPPH: 2,2-diphenyl-1- picrylhydrazyl; ESR: electron spin resonance spectroscopy; CAA: cell-based antioxidant assay; NADPH: nicotinamide adenine dinucleotide phosphate; GST: oxidase, glutathione S-transferase; GPX: glutathione peroxidase; Fe-NTA: ferric nitrilotriacetate; AAPH: 2,2- azobis(2-amidinopropane) dihydrochloride; LP: lipid peroxidation; LOX: lipoxygenase; XO: xanthine oxidase; Q7GA: quercetin-7-O-glucuronide; Q3′GA: quercetin-3′-O-glucuronide; Q4′GA: quercetin-4′-O-glucuronide; Q3S: quercetin-3-O-sulfate; DOPAC: 3,4-dihydroxyphenylacetic acid; protocatechuic acid, PCA: 3,4-dihydroxybenzoic acid; 3-OPAC: 3-hydroxyphenyl acetic acid; CYP1A1: cytoprotective enzyme (cytochrome P450 1A1); HO-1: heme oxygenase 1; QR1: quinone reductase; 1GST: glutathione S-transferase; GCLC: glutamate-cysteine ligase catalytic subunit; 3ʹME7G: 3ʹ-O-methyl-(-)-epicatechin-7-O-glucuronide; E3ʹG: (-)-epicatechin-3ʹ-O-glucuronide; E7G: (-)-epicatechin-7-O-glucuronide; 4ʹME3ʹG: 4ʹ-O-methyl-(-)-epicatechin-3ʹ-O-glucuronide; COPD: chronic obstructive pulmonary disease; LDL: low-density lipoprotein; NBT: nitroblue tetrazolium; PAMPs: pathogen-associated molecular patterns; DAMPs: damage-associated molecular patterns; PRRs: pattern recognition receptors; TLR4: toll-like receptor 4; ERK: extracellular signal-regulated protein kinases; LT: leukotrienes; Pg-3-glc: pelargonidin-3-O-glucoside; PGA: phloroglucinaldehyde; 4-HBA: 4-hydroxybenzoic acid; HUVECs: human umbilical vein endothelial cells; APC: antigen-presenting cells; MHC: major histocompatibility complex; TCR: T cell receptor; PCA: passive cutaneous anaphylaxis; FcεRI: high affinity Immunoglobulin E receptor; EGCG4″Me: (-)-epigallocatechin-3-O-(4-O-methyl)gallate; EGCG3″Me: (-)-epigallocatechin-3-O-(3-O-methyl)gallate; 67LR: 67 kDa laminin receptor; MRLC: myosin II regulatory light chain; CGA: chlorogenic acid; IFN-c: interferon-c; NGC: naringenin chalcone. [ABSTRACT FROM AUTHOR]

Food allergy (FA) is a serious food safety and public health issue. Increasing evidence has shed new light on significant interference of gut microbiome with mechanisms involved in the pathophysiology and progression of FA. New insights into the crosstalk between food components and the gut microbiome enable the development of viable strategies for inducing oral tolerance and modulating immune homeostasis. In this review, we first provide a brief outline of the observational evidence that supports associations between microbial exposures and FA, followed by an elaborated description of causation and the mechanisms by which the gut microbiome regulates FA. Subsequently, we highlight in detail how specific food components, pre- and probiotics can modulate the gut microbiome-immune axis and, consequently, modify the development of FA. The gut microbiome is a critical factor affecting FA susceptibility, and its regulatory mechanism is primarily through increasing protective Tregs and enhancing the intestinal mucosal barrier. The intake of high-fiber, tryptophan-rich diet and supplementation of diet with n-3PUFAs, polyphenols, pre- and probiotics, which are known to modulate gut microbiota towards to beneficial outcomes, while avoiding high-fat foods that trigger dysbiosis, can not only provide a potential approach to reduce the risk of FA in a primary prevention setting, but may also be a promising therapeutic strategy. This paper will contribute to dovetail food intervention strategies and bacterial therapeutics to modulate the immune system of allergic individuals in such a way that FA can be prevented and FA symptoms mitigated. • The correlations and causal relationships between the gut microbiome and FA are outlined. • The potential of microbiota-based dietary interventions for the prevention and treatment of FA is discussed. • The fiber/n-3 PUFAs/tryptophan/polyphenol-rich foods have anti-allergic effects. • Pre-/probiotics and FA-associated characteristic bacteria need to be further explored. • The precision microbial therapy of FA requires further research. [ABSTRACT FROM AUTHOR]

This retraction relates to this paper Xing Y, Zhang J, Xu H. I Onco Targets Ther i . 2016;9:3939-3949. Specifically, Images from Figure 3C, Migration, Treg-C+S and Migration, GIST882-sorafenib have been duplicated. [Extracted from the article]

The Th17/ Treg axis is a crucial regulator of anti-inflammatory and proinflammatory pathways that play fundamental roles in cancer and autoimmune diseases. The alteration of the Th17/Tregs axis is highly significant for developing novel therapeutic approaches. Th17 and Treg cells share a large portion of their transcriptome, albeit with distinct functions. The mechanisms governing the bifurcation of Th17 /Treg axis differentiation from naïve T cells are not yet understood. This study aims to identify the differentially expressed genes (DEGs) and gene-enriched pathways that contribute to the distinction between these closely aligned phenotypes. We analyzed RNA sequencing data of CD4+ T cells differentiated in vitro into Th0, Th17, and Tregs phenotypes and built gene enrichment networks. We studied the network rewiring of Th17 and Tregs from Th0 cells. In addition to common pathways and genes that are equally expressed between these two distinct phenotypes, we identified key genes and pathways that contribute to their distinctiveness. For example, the Keap1 gene and several of its interactors such as MCC1 were upregulated in Tregs indicating that Tregs possess mechanisms that prevent the over-activation of antioxidants pathways. Tregs also possess several genes that are involved in the hydrolysis of ATP to ADP as RAB37, ATP1A2, ATP1B, and PDE2A to ensure Treg anti-inflammatory capabilities. Additionally, one of the pathways that ensure Tregs differentiation and function seems to point toward an insulin role mediated by APOL9B and GOLM. Taken together our findings shed light on various essential regulators of the Th17/Treg axis and pave the way for treatment strategies that selectively target one phenotype while sparing the other. [ABSTRACT FROM AUTHOR]

• The importance of drug delivery timing and dosage in chemoimmunotherapy has been studied on a new model proposed in the paper. • The optimal controller is designed to reduce cancer cells for a lower dosage of immunotherapy and a fixed dosage of chemotherapy. • The suggested optimal timing and dosage of immunotherapy is able to reduce cancer cells, with less amount of drug injection compared to a fixed protocol. • The achievement of this paper could be the basis for designing new clinical trials. There are various approaches to control a mathematical dynamic of cancer, each of which is suitable for a special goal. Optimal control is considered as an applicable method to calculate the minimum necessary drug delivery in such systems. In this paper, a mathematical dynamic of cancer is proposed considering tumor cells, natural killer cells, CD8+ T cells, circulating lymphocytes, IL-2 cytokine and Regulatory T cells as the system states, and chemotherapy, IL-2 and activated CD8+ T cells injection rate as the control signals. After verifying the proposed mathematical model, the importance of the drug delivery timing and the effect of cancer cells initial condition are discussed. Afterwards, an optimal control is designed by defining a proper cost function with the goal of minimizing the number of tumor cells, and two immunotherapy drug amounts during treatment Results show that inappropriate injection of immunotherapy time schedule and the number of initial conditions of cancer cells might result in chemoimmunotherapy failure and auxiliary treatment must be prescribed to decrease tumor size before any treatment takes place. The obtained optimal control signals show that with lower amount of drug delivery and a suitable drug injection time schedule, tumor cells can be eliminated while a fixed immunotherapy time schedule protocol fails with larger amount of drug injection. This conclusion can be utilized with the aim of personalizing drug delivery and designing more accurate clinical trials based on the improved model simulations in order to save cost and time. [ABSTRACT FROM AUTHOR]

We read with great interest the paper by Dong et al.[1] on the association between metabolic obesity and the progression of knee osteoarthritis (OA) in elderly community residents. Metabolic syndrome, its components, and knee osteoarthritis: the Framingham osteoarthritis study. Moreover, it would be interesting to explore whether findings in this study on knee OA may be generalized into other large-joint OA, including hip OA, and other OA-involve joints, such as hand OA or temporomandibular joint OA.[5] The authors defined participants with metabolic syndrome through blood tests that were drawn at baseline. [Extracted from the article]

In this Special Issue of I Cells i , entitled "Immunomodulation by Mesenchymal Stem Cells 2020", you can find five excellent papers on the role of mesenchymal stem/stromal cells (MSCs) in immunomodulation, which also includes regenerative processes, such as wound healing. Although the precise mechanism of action (MOA) of these cells in various clinical applications is not fully understood, recent progress has been made in the functional characterisation of MSCs and their extracellular vesicles, especially in the perinatal field [[3], [5]], which can easily been translated to adult MSCs. 10.3390/cells10020280 9 Fiori A., Uhlig S., Kluter H., Bieback K. Human Adipose Tissue-Derived Mesenchymal Stromal Cells Inhibit CD4+ T Cell Proliferation and Induce Regulatory T Cells as Well as CD127 Expression on CD4+CD25+ T Cells. [Extracted from the article]

[Display omitted] • IDO1 induces immune tolerance within TME. • Serum profiling of IDO1 metabolites is of prognostic value. • IDO1 upregulation occurs after ICI therapy. • IDO1 inhibitors can be used safely with ICI therapy. • Epacadostat plus ICI renders promising clinical responses. • Clinical efficacy of anti-PD-L1/IDO inhibitor vaccination is promising. Metabolic alterations occur commonly in tumor cells as a way to adapt available energetic sources for their proliferation, survival and resistance. Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular enzyme catalyzing tryptophan degradation into kynurenine. IDO1 expression shows a rise in the stroma of many types of human cancers, and it provides a negative feedback mechanism for cancer evasion from immunosurveillance. Upregulation of IDO1 correlates with cancer aggression, poor prognosis and shortened patient survival. The increased activity of this endogenous checkpoint impairs effector T cell function, increases regulatory T cell (Treg) population and induces immune tolerance, so its inhibition potentiates anti-tumor immune responses and reshapes immunogenic state of tumor microenvironment (TME) presumably through normalizing effector T cell activity. A point is that the expression of this immunoregulatory marker is upregulated after immune checkpoint inhibitor (ICI) therapy, and that it has inducible effect on expression of other checkpoints. These are indicative of the importance of IDO1 as an attractive immunotherapeutic target and rationalizing combination of IDO1 inhibitors with ICI drugs in patients with advanced solid cancers. In this review, we aimed to discuss about the impact of IDO1 on tumor immune ecosystem, and the IDO1-mediated bypass of ICI therapy. The efficacy of IDO1 inhibitor therapy in combination with ICIs in advanced/metastatic solid tumors is also a focus of this paper. [ABSTRACT FROM AUTHOR]

• A model is proposed based on the key role of Regulatory T cells in chemoimmunotherapy. • The model's fixed points are obtained and the bifurcation diagrams are discussed. • New features of personalizing a cancer mathematical model are presented. • Considering Regulatory T cells leads to identifying critical patient conditions more precisely. Studying the mathematical dynamics of cancer has gained the attention of bioengineers in the past three decades. Different kinds of modelling considering various aspects of treatment have been proposed. In this paper, the key role of Regulatory T cells is discussed and a model in ordinary differential equation (ODE) form is proposed by adding this state to the system dynamics considering chemoimmunotherapy treatment. Regulatory T cells are considered as one of the main tumor cells' tactics to deceive the body's immune system. The improved model is verified mathematically and biologically and fits all criteria in both fields. The results show that entering Regulatory T cells state on cancer mathematical modelling for simulating body cells for chemoimmunotherapy provides a way to identify critical cases more carefully, which a simplified model is unable to accomplish. This point emphasizes the fact that this state must be present in cancer modelling to anticipate immune response more accurately. The advanced system fixed points are obtained by the Newton method and bifurcation diagrams are derived and discussed. New features and remarks are proposed during the journey of developing more accurate models that have the best fit with laboratory data. The sensitivity chart of the model is illustrated and novel aspects of discussions are made with the aim of personalizing a model for a patient and identifying critical conditions based on the chart before any treatment begins. This point enables physicians to determine whether critical conditions have occurred for a patient in a specific treatment or not. [ABSTRACT FROM AUTHOR]

33921711 7 Demosthenous C., Sakellari I., Douka V., Papayanni P.G., Anagnostopoulos A., Gavriilaki E. The Role of Myeloid-Derived Suppressor Cells (MDSCs) in Graft-versus-Host Disease (GVHD). Moreover, Papafragkos et al. have reviewed the current literature concerning MDSCs in lymphoid malignancies in their paper entitled " I Decoding the Myeloid-Derived Suppressor Cells in Lymphoid Malignancies i ". Another interesting field, that of the graft-versus-host disease (GVHD), is covered in the review paper of Demosthenous et al., entitled " I The Role of Myeloid-Derived Suppressor Cells (MDSCs) in Graft-versus-Host Disease (GVHD) i ". [Extracted from the article]

Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research. [Display omitted] [ABSTRACT FROM AUTHOR]

The newly discovered subset of memory T cells, tissue resident memory T (TRM) cells, reside in peripheral tissues for a long time, contributing to a rapid immune response and constituting the first line of defense when pathogens invade cells. Tissue resident memory T cells have unique transcriptome characteristics, and their presence in peripheral tissues is regulated by many factors. TRM cells residing in different tissues often express different surface markers. In addition to CD8+ and CD4+ T cells, which are the best-characterized T cells, Treg cells and various innate T cells can reside in nonlymphoid tissues. Many recent studies have shown that tissue resident memory T cells play indispensable roles in tumor immunity and allergic diseases. This paper reviews the differentiation, regulation, variety and function of TRM cells and the roles they play in skin diseases, including cutaneous melanoma and psoriasis. • Tissue-resident memory T cells exhibit distinct tissue-specific and niche-specific functions in immune detection network. • Multiple factors control the development and resident of Tissue-resident memory T cell. • Tissue-resident memory T cells participate in skin inflammation and contribute tomaintaining the recurrence of skin diseases. [ABSTRACT FROM AUTHOR]

A recent paper by Shi et al. defines the role of regulatory T cells (Tregs) in white matter recovery after ischemic stroke. This study elucidates the mechanisms by which Tregs direct microglia to alter their phenotype to support oligodendrogenesis, thereby improving white matter integrity and functional recovery after stroke in mice. [ABSTRACT FROM AUTHOR]

A failure of central immune tolerance driven by autoantigen specific T regulatory (Treg) cells is a major cause of many autoimmune diseases. Restoration of proper autoantigen Treg specific response holds promise as a highly effective, long-term therapy for a wide variety of autoimmune diseases. Generating autoantigen specific Tregs remains a challenge due to the non-specific nature of most tolerizing agents and the complexities of generating Tregs in vivo. Here we show a new push/pull method for inducing antigen-specific Treg tolerance via induction of tolerogenic dendritic cells (tolDCs). We identified a combination of three tolerogenic drugs, dexamethasone, simvastatin and SC-514, which when used in combination with toll-like-receptor (TLR) agonists induces an active tolDC phenotype. When the tolerogenic combination was packaged into a liposome with a model antigen such as ovalbumin (OVA), these tolDCs induce differentiation of OVA specific Tregs both ex vivo and in vivo. We examined the tolerizing potential of the combination in an experimental autoimmune encephalomyelitis (EAE) disease model. Given the antigen specificity of this technique, this paper presents an attractive preclinical autoimmune therapy. [ABSTRACT FROM AUTHOR]

This paper aimed to explore the roles of the combination of electroacupuncture (EA) and induced pluripotent stem cell-derived small extracellular vesicles (iPSC-EVs) on mice with ischemic stroke and the underlying mechanisms. A focal cerebral ischemia model was established in C57BL/6 mice through middle cerebral artery occlusion (MCAO). After 3 days, neurological impairment and motor function were examined by performing behavioral tests. The infarct volume and neuronal apoptosis were examined using TTC staining and TUNEL assays. Flow cytometry was performed to assess the proliferation of T lymphocytes. The changes in the interleukin (IL)-33/ST2 axis were evaluated by immunofluorescence and Western blotting. The combination of EA and iPSC-EVs treatment ameliorated neurological impairments and reduced the infarct volume and neuronal apoptosis in MCAO mice. EA plus iPSC-EVs suppressed T helper (Th1) and Th17 responses and promoted the regulatory T cell (Treg) response. In addition, EA plus iPSC-EVs exerted neuroprotective effects by regulating the IL-33/ST2 axis and inhibiting the microglia and astrocyte activation. Taken together, the study shows that EA and iPSC-EVs exerted a synergistic neuroprotective effect in MCAO mice, and this treatment may represent a novel potent therapy for ischemic stroke and damage to other tissues. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is classified as the third leading cancer globally and one of the major causes of morbidity and mortality around the world. The interaction of the immune system with the cancer cells plays a vital role in CRC progression. Regulatory T cells (Tregs) are a form of T cells, which regulate and suppress unwanted activation of the immune system and play a major role in preventing autoimmune diseases. Tregs exhibit a significant role in immune modulation during CRC progression through accumulation in the tumor microenvironment (TME) and suppression of immunity against tumor specific antigens promoting tumor progression. The role of Tregs in CRC progression and its interaction with other immune cells within CRC TME and current clinical trials were reviewed in this paper. [Display omitted] • Discusses the role of Tregs in immune modulation during CRC progression. • Explores the role of Tregs in CRC tumor microenvironment. • Highlights the mechanism of Tregs in CRC growth and metastasis. • Identifies and discusses current clinical trials targeting Tregs in CRC therapy. [ABSTRACT FROM AUTHOR]

The autoimmune reaction against the beta cells of the pancreatic islets in type 1 diabetes mellitus (T1DM) patients is active in prediabetes and during the development of the clinical manifestation of T1DM, but it decreases within a few years of the clinical manifestation of this disease. A key role in the pathogenesis of T1DM is played by regulatory T cell (Treg) deficiency or dysfunction. Immune interventions, such as potential therapeutic applications or the induction of the Treg-cell population in T1DM, will be important in the development of new types of treatment. The aim of this study was to evaluate innovative immune interventions as treatments for T1DM. After an evaluation of full-length papers from the PubMed database from 2010 to 2021, 20 trials were included for the final analysis. The analysis led to the following conclusions: Treg cells play an important role in the limitation of the development of T1DM, the activation or application of Tregs may be more effective in the early stages of T1DM development, and the therapeutic use of Treg cells in T1DM is promising but requires long-term observation in a large group of patients. [ABSTRACT FROM AUTHOR]

COVID-19 is a disease occurring as a result of infection by a novel coronavirus called SARS-CoV-2. Since the WHO announced COVID-19 as a global pandemic, mathematical works have taken place to simulate infection scenarios at different scales even though the majority of these models only consider the temporal dynamics of SARS-COV-2. In this paper, we present a new spatio-temporal within-host mathematical model of COVID-19, accounting for the coupled dynamics of healthy cells, infected cells, SARS-CoV-2 molecules, chemokine concentration, effector T cells, regulatory T cells, B-lymphocytes cells and antibodies. We develop a computational framework involving discretisation schemes for diffusion and chemotaxis terms using central differences and midpoint approximations within two dimensional space combined with a predict–evaluate–correct mode for time marching. Then, we numerically investigate the model performance using a list of values simulating the baseline scenario for viral infection at a cellular scale. Moreover, we explore the model sensitivity via applying certain conditions to observe the model validity in a comparison with clinical outcomes collected from recent studies. In this computational investigation, we have a numerical range of 104 to 108 for the viral load peak, which is equivalent to what has been obtained from throat swab samples for many patients. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans; therefore, a range of DC-based approaches have been established to promote an immune response against cancer cells. The efficacy of DC-based immunotherapeutic approaches is markedly affected by the immunosuppressive factors related to the tumor microenvironment, such as adenosine. In this paper, based on immunological theories and experimental data, a hybrid model is designed that offers some insights into the effects of DC-based immunotherapy combined with adenosine inhibition. The model combines an individual-based model for describing tumor-immune system interactions with a set of ordinary differential equations for adenosine modeling. Computational simulations of the proposed model clarify the conditions for the onset of a successful immune response against cancer cells. Global and local sensitivity analysis of the model highlights the importance of adenosine blockage for strengthening effector cells. The model is used to determine the most effective suppressive mechanism caused by adenosine, proper vaccination time, and the appropriate time interval between injections. [Display omitted] • We propose a hybrid model to describe the immunosuppressive function of adenosine in tumor micro environment. • Our model provides immunologists with a new level of insight into the role of immunosuppressive factors of the immune system. • Our model highlights the importance of adenosine blockage for strengthening effector cells and suppressing Treg cells. • Model simulations are compatible with in vivo experimental data. • The results reveals that the appropriate time interval for administration of adenosine inhibitor is between 2 and 4 days. [ABSTRACT FROM AUTHOR]

The affiliation of the first author " B Youming Zhang b " and the authors "Yunli Shen, Qizheng Lu", should be B Affiliation 2 "Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, People's Republic of China." b And the affiliation of the author " B Zichun Cai b " should be B Affiliation 3 "Department of Cardiology, Shanghai East Hospital of Clinical Medical College, Nanjing Medical University, Nanjing 211166, People's Republic of China." Youming Zhang, Zichun Cai and Yunli Shen contributed equally to this paper Correction to: J Nanobiotechnol 19:271 (2021) https://doi.org/10.1186/s12951-021-01016-x Following publication of the original article [[1]], the authors identified some mistakes about the affiliations of the authors. [Extracted from the article]

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which, via unresolved mechanisms, platelets and megakaryocytes (MKs) are targeted by autoantibodies and/or T cells resulting in increased platelet destruction and impairment of MK function. Over the years, several therapeutic modalities have become available for ITP, however, therapeutic management has proven to be very challenging in several cases. Patients refractory to treatment can develop a clinically worsening disease course, treatment-induced toxicities and are predisposed to development of potentially life-endangering bleedings. It is therefore of critical importance to timely identify potential refractory patients, for which novel diagnostic approaches are urgently needed in order to monitor and predict specific therapeutic responses. In this paper, we propose promising diagnostic investigations into immune functions and characteristics in ITP, which may potentially be exploited to help predict platelet count responses and thereby distinguish therapeutic responders from non-responders. This importantly includes analysis of T cell homeostasis, which generally appears to be disturbed in ITP due to decreased and/or dysfunctional T regulatory cells (Tregs) leading to loss of immune tolerance and initiation/perpetuation of ITP, and this may be normalized by several therapeutic modalities. Additional avenues to explore in possible prediction of therapeutic responses include examination of platelet surface sialic acids, platelet apoptosis, monocyte surface markers, B regulatory cells and platelet microparticles. Initial studies have started evaluating these markers in relation to response to various treatments including glucocorticosteroids (GCs), intravenous immunoglobulins (IVIg) and/or thrombopoietin receptor agonists (TPO-RA), however, further studies are highly warranted. The systematic molecular analysis of a broad panel of immune functions may ultimately help guide and improve personalized therapeutic management in ITP. [ABSTRACT FROM AUTHOR]

Crohn's disease and ulcerative colitis, two major forms of inflammatory bowel disease (IBD) in humans, afflicted in genetically predisposed individuals due to dysregulated immune response directed against constituents of gut flora. The defective immune responses mounted against the regulatory mechanisms amplify and maintain the IBD-induced mucosal inflammation. Therefore, restoring the balance between inflammatory and anti-inflammatory immunepathways in the gut may contribute to halting the IBD-associated tissue-damaging immune response. Phenotypic and functional characterization of various immune-suppressive T cells (regulatory T cells; Tregs) over the last decade has been used to optimize the procedures for in vitro expansion of these cells for developing therapeutic interventional strategies. In this paper, we review the mechanisms of action and functional importance of Tregs during the pathogenesis of IBD and modulating the disease induced inflammation as well as role of mouse models including humanized mice repopulated with the human immune system (HIS) to study the IBD. "Humanized" mouse models provide new tools to analyze human Treg ontogeny, immunobiology, and therapy and the role of Tregs in developing interventional strategies against IBD. Overall, humanized mouse models replicate the human conditions and prove a viable tool to study molecular functions of human Tregs to harness their therapeutic potential. [ABSTRACT FROM AUTHOR]