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• E-MPBs shows sustained cellular uptake by microglia. • E-MPBs exhibits anti-ROS and anti-inflammation properties against M1 microglia. • E-MPBs develops a novel nanoplatform for SCI. Developing biomimetic nanoparticles without off-target side-effects remains a major challenge in spinal cord injury (SCI) immunotherapy. In this paper, we have conducted a drug carrier which is biocompatible macrophages-exocytosed exosome-biomimetic manganese (Mn)-iron prussian blue analogues (MPBs) for SCI immunotherapy. Exosome-sheathed MPBs (E-MPBs) exhibit promoted microglia accumulation, alleviation from H 2 O 2 -induced microenvironment and inhibition of apoptosis and inflammation in vitro. In addition, E-MPBs possessed significant tissue repair and neuroprotection in vivo. These properties endowed E-MPBs with great improvement in vivo in function recovery, resulting in anti-neuroinflammation activity and excellent biocompatibility in mice SCI model. As a promising treatment for efficient SCI immunotherapy, these results demonstrate the use of exosome-sheathed biomimetic nanoparticles exocytosed by anti-inflammation cells is feasible. [ABSTRACT FROM AUTHOR]

Abstract As antigen-presenting cells (APC), B cells exert a variety of immune regulatory functions mainly by presenting antigens, triggering immune response, and producing antibodies for immune regulation. Regulatory B cells (Bregs) are special subpopulations of B cells with immune-regulating or immune-suppressing properties and play a role in peripheral tolerance. Bregs suppress immune response through inhibiting the differentiation of dendritic cells (DCs), suppressing the proliferation of helper T1(TH1) cells and helper T17 (TH17) cells, inducing the differentiation of fork head transcription factor p3 positive regulatory T cells (FoxP3+ Tregs). Different subsets of Bregs have distinct phenotypes and markers. Different subsets of Bregs participate in immune modulation by different ways. The absence or loss of Bregs exacerbates the severity of many disease such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and graft-versus-host-disease (GVHD). Bregs are also involved in tumor immunosuppressive effect and inhibit the antitumor immune process. In this article, we review the research advances of Bregs in autoimmune diseases, GVHD and tumor. Highlights • Previous studies have shown that regulatory B cells play important roles in inflammatory diseases and tumor. • There is no systematic review of the role of regulatory B cells in inflammatory diseases and tumor. • In this paper, the role of regulatory B cells in inflammatory diseases and tumors is systematically reviewed. • This article provides researchers with the latest systematic research of regulatory B cells. [ABSTRACT FROM AUTHOR]

Abstract Development of active compounds to control inflammation against systemic inflammatory response syndrome (SIRS) is critical important. Dioscin shows anti-inflammatory effects in our previous works. However, the action of the compound on SIRS still remained unknown. In the present paper, zymosan induced generalized inflammation (ZIGI) models in mice and rats, and PMA-differentiated THP‑1 cells stimulated by lipopolysaccharide (LPS) and Pam3-Cys-Ser-Lys4 (Pam3CSK4) were used. The results showed that dioscin significantly inhibited the proliferation of THP‑1 cells stimulated by LPS and Pam3CSK4, obviously reduced the soakage of inflammatory cells and necrosis in liver, kidney and intestine of rats and mice, and reduced peritoneal ascites fluid compared with ZIGI model groups. In addition, dioscin significantly declined the levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cr), blood urea nitrogen (BUN), malondialdehyde (MDA) and myeloperoxidase (MPO), increased the levels of superoxide dismutase (SOD) in rats and mice. The migration of macrophages in tissues was also suppressed by dioscin. Mechanism investigation showed that dioscin significantly inhibited the expression levels of TLR2, MyD88, NF‑κb, HMGB‑1, increased the expression levels of IKBα, and decreased the mRNA levels of interleukin‑1 beta (IL‑1β), interleukin‑6 (IL‑6) and tumor necrosis factor‑alpha (TNF‑α) in liver, kidney, intestine tissues of rats and mice, and in PMA-differentiated THP‑1 cells, which were further confirmed by TLR2 siRNA silencing in vitro. In conclusion, our data confirmed that dioscin exhibited protective effects against SIRS via adjusting TLR2/MyD88 signal pathway, which should be developed as one potent candidate to treat SIRS in the future. Graphical abstract Unlabelled Image Highlights • Dioscin significantly inhibited the proliferation of THP‑1 cells stimulated by LPS. • Dioscin showed protective effects against SIRS in mice and rats. • Dioscin suppressed the migration of macrophages in tissues of rats and mice. • Dioscin adjusted TLR2/MyD88 pathway in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Emerging evidence reveals the controversial role of B cells in antitumor immunity, but the underlying mechanisms have to be explored. Three latest articles published in the issue 521 of Nature in 2015 reconfirmed the puzzling topic and put forward some explanations of how B cells regulate antitumor T-cell responses both positively and negatively. This paper attempts to demonstrate that different B-cell subpopulations have distinct immunological properties and that they are involved in either antitumor responses or immunosuppression. Recent studies supporting the positive and negative roles of B cells in tumor development were summarized comprehensively. Several specific B-cell subpopulations, such as IgG(+), IgA(+), IL-10(+), and regulatory B cells, were described in detail. The mechanisms underlying the controversial B-cell effects were mainly attributed to different B-cell subpopulations, different B-cell-derived cytokines, direct B cell-T cell interaction, different cancer categories, and different malignant stages, and the immunological interaction between B cells and T cells is mediated by dendritic cells. Promising B-cell-based antitumor strategies were proposed and novel B-cell regulators were summarized to present interesting therapeutic targets. Future investigations are needed to make sure that B-cell-based pharmacological strategies benefit cancer immunotherapy substantially. [ABSTRACT FROM AUTHOR]

• New advancement for development of optimal and safe delivery route for oncolytic viruses. • Diverse platforms, such as employment of cells and nanoparticles to protect the virus from antiviral neutralization and improve the oncolytic potential of viruses. • Efficient systematic delivery of oncolytic viruses enables the expansion of their application toward cancer therapy. • Development of novel methods to make oncolytic viruses more resistant to undesirable reactions of the host's immune system. Oncolytic viruses (OVs) harness the hallmarks of tumor cells and cancer-related immune responses for the lysis of malignant cells, modulation of the tumor microenvironment, and exertion of vaccine-like activities. However, efficient clinical exploitation of these potent therapeutic modules requires their systematic administration, especially against metastatic and solid tumors. Therefore, developing methods for shielding a virus from the neutralizing environment of the bloodstream while departing toward tumor sites is a must. This paper reports the latest advancements in the employment of chemical and biological compounds aimed at safe and efficient delivery of OVs to target tissues or tumor deposits within the host. [ABSTRACT FROM AUTHOR]

THP-1 is a human leukemia monocytic cell line, which has been extensively used to study monocyte/macrophage functions, mechanisms, signaling pathways, and nutrient and drug transport. This cell line has become a common model to estimate modulation of monocyte and macrophage activities. This review attempts to summarize and discuss recent publications related to the THP-1 cell model. An overview on the biological similarities and dissimilarities between the THP-1 cell line and human peripheral blood mononuclear cell (PBMC) derived-monocytes and macrophages, as well as the advantages and disadvantages of the use of THP-1 cell line, is included. The review summarizes different published co-cultivation studies of THP-1 cells with other cell types, for instance, intestinal cells, adipocytes, T-lymphocytes, platelets, and vascular smooth muscle cells, which can be an option to study cell–cell interaction in vitro and can be an approach to better mimic in vivo conditions. Macrophage polarization is a relatively new topic which gains interest for which the THP-1 cell line also may be relevant. Besides that an overview of newly released commercial THP-1 engineered-reporter cells and THP-1 inflammasome test-cells is also given. Evaluation of recent papers leads to the conclusion that the THP-1 cell line has unique characteristics as a model to investigate/estimate immune-modulating effects of compounds in both activated and resting conditions of the cells. Although the THP-1 response can hint to potential responses that might occur ex vivo or in vivo, these should be, however, validated by in vivo studies to draw more definite conclusions. [ABSTRACT FROM AUTHOR]

Dehydroepiandrosterone (DHEA), the most plentiful steroid hormone, has been convincingly known to have many biological effects and diverse influence in various types of cells, tissues and organs. The effects of DHEA on the humoral and cellular immune response are widely tested, but it is unclear whether DHEA itself serves as an activator of immune function and the literature pertaining to the in vitro effects of DHEA remains contested. In the present paper, the effects of DHEA on the thymocytes in vitro were studied. The results showed that DHEA could enhance the expression of Fas and Fas-L and induce thymocyte apoptosis. This suggests that dehydroepiandrosterone may induce the apoptosis of thymocyte through Fas/Fas-L pathway. [Copyright &y& Elsevier]

Type 1, or cellular, immune response is characterized by overproduction of TNF-α, IFN-gamma, IL-1, IL-2 and IL-8 and is the underlying immune mechanism of psoriasis, alopecia areata, rheumatoid arthritis, Crohn''s disease, multiple sclerosis, insulin-dependent diabetes mellitus and experimental autoimmune uveitis (EAU). Type 2 immune response is seen in antibody-mediated autoimmune diseases. Based on the pharmacokinetic effects of cetirizine and allopurinol, this paper introduces these two safe and inexpensive drugs as novel potential agents against cell-mediated autoimmune disorders.Cetirizine, supposed to inhibit DNA binding activity of NF-kappa B, inhibits the expression of adhesion molecules on immunocytes and endothelial cells and the production of IL-8 and LTB4, two potent chemoattractants, by immune cells. It induces the release of PGE2, a suppressor of antigen presentation and MHC class II expression, from monocyte/macrophages and reduces the number of tryptase positive mast cells in inflammation sites. Tryptase is a chemoattractant, generates kinins from kininogen, activates mast cells, triggers maturation of dendritic cells and stimulates the release of IL-8 from endothelial cells and the production of Th1 lymphokines by mononuclear immunocytes.Allopurinol is a free radical scavenger, suppresses the production of TNF-α and downregulates the expression of ICAM-1 and P2X7 receptors on monocyte/macrophages. ICAM-1 serves as a ligand for LFA-1 (on T lymphocytes), allowing proper antigen presentation. P2X7 receptors are thought to be involved in IL-1β release, mitogenic stimulation of T lymphocytes and the probable cytoplasmic communication between macrophages and lymphocytes at inflammation sites.Allopurinol was markedly more effective than prednisolone in treating experimental autoimmune uveitis and in combination with cyclosporine suppressed the inflammatory reaction of this condition more effectively than either agent alone.As allopurinol is a competitive inhibitor of xanthine oxidase and decreases serum levels of uric acid, which is protective against multiple sclerosis, it should preferably be coadministered with uric acid precursors in the treatment of this condition.Cetirizine and allopurinol may prove of benefit in the treatment of various cellular autoimmune disorders. [Copyright &y& Elsevier]

• Generation and development of cholestasis is a highly immunogenic process. • Immune regulators, adaptive and innate immune cells all participate in this process. • Researches on mechanisms develop chemokines and cytokines into indicators of severity. • Immune components provide targets for the future therapeutics. Cholestasis is one of the most common clinical symptom of liver diseases. If patients do not receive effective treatment, cholestasis can evolve into liver fibrosis, cirrhosis and ultimately liver failure requiring liver transplantation. Currently, only ursodeoxycholic acid, obeticholic acid and bezafibrate are FDA-approved drugs, thereby requiring a breakthrough in new mechanisms and therapeutic development. Inflammation is one of the common complications of cholestasis. Hepatic accumulation of toxic hydrophobic bile acids is a highly immunogenic process involving both resident and immigrating immune cells. And the resulting inflammation may further aggravate hepatocyte injury. Though, great investigations have been made in the immune responses during cholestasis, the relationship between immune responses and cholestasis remains unclear. Moreover, scarce reviews summarize the immune responses during cholestasis and the efficacy of therapies on immune response. The main purpose of this paper is to review the existing literature on dysfunctional immune response during cholestasis and the effect of treatment on immune response which may provide an insight for researchers and drug development. [ABSTRACT FROM AUTHOR]

Abstract: In the past decade it has been established that regulatory T cells (Tregs) control all immune responses. As the induction and effector mechanisms used by Tregs are being unraveled, it is emerging that a reciprocal population of CD4+ T lymphocytes exists in the immune system that produces inflammatory cytokine IL-17, and coined "Th17 cells". Th17 cells have been implicated in the pathogenesis of many forms of human disease. The development, function, mechanism of action, and homeostasis of Tregs and Th17 cells, and the reciprocal control between Tregs and Th17 cells were presented at the Second International Conference on Regulatory T Cells and Th17 Cells and Clinical Application in Human Diseases in Shanghai on 17–20 July 2010 (China Tregs/Th17 2010). In this Special Issue of International Immunopharmacology, several paper submitted to the conference will highlight the biology of Tregs and Th17 cells, and their clinical application in human disease. [Copyright &y& Elsevier]

Abstract: Regulatory T cells (Tregs) are subsets of T cells that are specifically dedicated to controlling immune responses. It has been established that Tregs play a key role in regulating autoimmune disease, allergy, cancer, infectious disease, and in the induction of transplantation tolerance. The latest progress in the development, function, mechanism of action, and homeostasis of regulatory T cells, and their translation to the clinic were presented at the International Conference on Regulatory T Cells and Clinical Application in Human Diseases in Beijing on 25–27 October 2008 (China Tregs 2008). In this Special Issue of International Immunopharmacology, several papers submitted to the China Tregs 2008 will highlight some of the recent advances in the biology of regulatory T cells and current strategies to translate regulatory T cells into the clinic. [Copyright &y& Elsevier]

The new coronavirus outbreak is an ongoing pandemic that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new coronavirus SARS-Cov-2 belongs to the subfamily of β–coronaviruses and shares 79.5% of the genetic sequence of SARS-CoV, the causative agent of the epidemic that started in 2002 and ended in 2004. Considering the clinical impact of the new outbreak, it is highly important to study the potential responses of the human immune system during the SARS-CoV-2 infection as well as the role of virus-specific T cells and by B-lymphocytes. Moreover, specific data on the production of IgG and IgM is crucial to allow the rapid identification of the infection. In this paper we also described the importance of sensitive and specific rapid test for SARS-CoV-2. Indeed, this test represents an important immunological tool aimed at identifying the precise phase of the infection in order to undertake a more appropriate pharmacological treatment. Lastly, we provided an overview of pharmacological treatments aimed to reduce inflammatory processes underlying the infection and the need for the discovery of a new vaccine against SARS-CoV-2. [ABSTRACT FROM AUTHOR]