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Dysregulation of the immune response plays an important role in the progression of SARS-CoV-2 infection. A "cytokine storm", which is a phenomenon associated with uncontrolled production of large amounts of cytokines, very often affects patients with COVID-19. Elevated activity of chemotactic cytokines, called chemokines, can lead to serious consequences. CXCL10 has an ability to activate its receptor CXCR3, predominantly expressed on macrophages, T lymphocytes, dendritic cells, natural killer cells, and B cells. So, it has been suggested that the chemokine CXCL10, through CXCR3, is associated with inflammatory diseases and may be involved in the development of COVID-19. Therefore, in this review paper, we focus on the role of CXCL10 overactivity in the pathogenesis of COVID-19. We performed an extensive literature search for our investigation using the MEDLINE/PubMed database. Increased concentrations of CXCL10 were observed in COVID-19. Elevated levels of CXCL10 were reported to be associated with a severe course and disease progression. Published studies revealed that CXCL10 may be a very good predictive biomarker of patient outcome in COVID-19, and that markedly elevated CXCL10 levels are connected with ARDS and neurological complications. It has been observed that an effective treatment for SARS-CoV-2 leads to inhibition of "cytokine storm", as well as reduction of CXCL10 concentrations. It seems that modulation of the CXCL10–CXCR3 axis may be an effective therapeutic target of COVID-19. This review describes the potential role of CXCL10 in the pathogenesis of COVID-19, as well as its potential immune–therapeutic significance. However, future studies should aim to confirm the prognostic, clinical, and therapeutic role of CXCL10 in SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Aim: The objective of this review is to describe the immunological mechanisms which facilitate maternal tolerance at the maternal‐placental interface, and to discuss how these mechanisms are disrupted in pre‐eclampsia. Methods: A literature review was performed based on the analysis of papers available on PubMed. The most important and relevant studies regarding the immunological mechanisms which facilitate maternal tolerance in healthy pregnancy and pre‐eclampsia are presented in this article. Results: The maternal‐placental interface is the site where the immune tolerance begins and develops. Within the innate immunity, natural killer cells, macrophages and dendritic cells play a pivotal role in tolerance through regulation of inflammation. On the other hand, within the adaptive immunity, the correct increase of regulatory T cells is crucial for ensuring immune tolerance toward placental cells. Disturbances in maternal tolerance can lead to the appearance of pregnancy complications such as pre‐eclampsia, which has a considerable impact on perinatal morbidity and mortality. Conclusion: Our partial knowledge of immunological mechanisms involved in tolerance at the maternal‐placental interface indicates that pre‐eclampsia is characterized by alterations of this maternal immune tolerance, which could represent the origin of the disease. [ABSTRACT FROM AUTHOR]

• Nanocellulose is a biocompatible material, suitable for biomedical applications. • Cellulose Nanocrystals can induce proinflammatory response by activating macrophages. • Cellulose Nanofibers can induce tolerogenic properties of dendritic cells. • Surface modification of nanocellulose changes its immunomodulatory properties. Cellulose is the most abundant natural polymer in the world. Nanoscale forms of cellulose, including cellulose nanofibers (CNF), cellulose nanocrystals (CNC) and bacterial nanocellulose (BC), are very attractive in industry, medicine and pharmacy. Biomedical applications of nanocellulose in tissue engineering, regenerative medicine, and controlled drug delivery are the most promising. Nanocellulose is considered a biocompatible nanomaterial and relatively safe for biomedical applications. However, more studies are needed to prove this hypothesis, especially those related to chronic exposure to nanocellulose. Besides toxicity, the response of the immune system is of particular importance in this sense. This paper provides a comprehensive and critical review of the current-state knowledge of the impact of nanocellulose on the immune system, especially on macrophages and dendritic cells (DC), as the central immunoregulatory cells, which has not been addressed in the literature sufficiently. Nanocellulose, especially CNC, can induce the inflammatory response upon the internalization by macrophages, but this reaction may be significantly modulated by introducing different functional groups on their surface. Our original results showed that nanocellulose has a potent immunotolerogenic potential. Native CNF potentiated the capacity of DC to induce conventional Tregs. When carboxyl groups were introduced on the CNF surface, the tolerogenic potential of DC was shifted towards the induction of regulatory CD8+ T cells, whereas the introduction of phosphonates on CNF surface potentiated DCs' capacity to induce both regulatory CD8+ T cells and Type 1 regulatory (Tr-1) cells. These results are extremely important when considering the application of nanocellulose in vivo , especially for tissue regeneration and wound healing. [ABSTRACT FROM AUTHOR]

Children surviving preterm birth have a high risk of disability, particularly cognitive and learning problems. There is extensive clinical and experimental evidence that disability is now primarily related to dysmaturation of white and gray matter, defined by failure of oligodendrocyte maturation and neuronal dendritic arborization, rather than cell death alone. The etiology of this dysmaturation is multifactorial, with contributions from hypoxia‐ischemia, infection/inflammation and barotrauma. Intriguingly, these factors can interact to both increase and decrease damage. In this review we summarize preclinical and clinical evidence that all of these factors trigger secondary or chronic inflammation and gliosis. Thus, we hypothesize that these shared pathological features play a key role in a final common pathway that leads to the impaired neural maturation and connectivity and cognitive/motor impairments that are commonly observed in infants born preterm. This raises the possibility that secondary or chronic inflammation may be a viable therapeutic target for delayed interventions to improve neurodevelopmental outcomes after preterm birth. What this paper adds: Hypoxia‐ischemia, infection/inflammation, and barotrauma/volutrauma all contribute to preterm brain injury. Multiple different triggers of preterm brain injury are associated with central nervous system dysmaturation. Secondary brain inflammation may be a viable target to improve neurodevelopment after preterm birth. [ABSTRACT FROM AUTHOR]

The ability of mesenchymal stromal cells (MSCs) to suppress immune responses combined with their potential to actively participate in tissue repair provides a strong rationale for the use of MSCs as a new treatment option in diseases characterized by inflammation and severe tissue damage, such as Crohn's disease (CD) and perianal fistulas. Multiple studies have shown that MSCs suppress a range of immune cells, such as dendritic cells (DC), naïve and effector T cells, and natural killer (NK) cells. Recently published papers attribute the immunosuppressive capacity of MSCs to soluble factors produced by MSCs, such as prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO). Promising results are obtained from phase I and II clinical trials with autologous and allogeneic MSCs as treatment for refractory CD and perianal fistulas; however the question remains: what are the molecular mechanisms underlying the immunomodulating properties of MSCs? This paper highlights the present knowledge on the immunosuppressive effects of MSCs and its complexity in relation to CD and perianal fistulas. [ABSTRACT FROM AUTHOR]

Abstract: Oil-in-water emulsions are used as vaccine adjuvants, but the mechanism of action remains unknown. In this paper we used phagocytes (monocytes, macrophages, dendritic cells) and non-phagocytic cells (fibroblasts, skeletal muscle cells) to study internalization of emulsions in vitro, and to characterize the influence of emulsion uptake on cellular metabolism of neutral lipids. We found that all tested cell types endocytose the emulsion droplets, and that the uptake leads to an acute accumulation of neutral lipids in the form of cytoplasmic lipid droplets. The accumulated lipids comprise not only the delivered squalene, but also cholesteryl esters, triacylglycerols, fatty acids, and diacylglycerols. Lipid metabolism and innate immunity are closely linked, and accumulation of lipids in non-adipose tissues is known to induce inflammatory conditions. We propose that one aspect of o/w emulsion adjuvanticity could depend on their ability to rapidly change lipid metabolism of the target cells. [Copyright &y& Elsevier]

In vivo confocal microscopy (IVCM) of the living human cornea offers the ability to perform repeated imaging without tissue damage. Studies using corneal IVCM have led to significant contributions to scientific and clinical knowledge of the living cornea in health and pathological states. Recently the application of corneal IVCM beyond ophthalmology to wider clinical and research fields has been demonstrated. Abnormalities of the corneal subbasal nerve plexus have been associated with many forms of peripheral neuropathy and Langerhans cells correlate with systemic inflammatory states. There is a rapidly growing evidence base investigating the use of corneal IVCM in many systemic conditions and a well-established evidence base for IVCM imaging of the corneal subbasal plexus in diabetic peripheral neuropathy. This paper reviews the potential use of corneal IVCM in general clinical practice as a noninvasive method of assessing peripheral neuropathies, monitoring inflammatory states and clinical therapeutic response. [ABSTRACT FROM AUTHOR]

Tanshinone IIA (Tan II A) is widely used in the treatment of cardiovascular diseases as an active component of Salvia miltiorrhiza Bunge. It has been demonstrated to have pleiotropic effects for atherosclerosis. From the anti-inflammatory and immunomodulatory mechanism perspective, this paper reviewed major progresses of Tan IIA in antiatherosclerosis research, including immune cells, antigens, cytokines, and cell signaling pathways. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) play an important role in both immunological tolerance and immunity as well as in pro- and anti-inflammatory responses. Upon uptake of apoptotic cells and apoptotic bodies, DCs degrade self antigens from them and induce anti-inflammatory response and T regulatory (Treg) cells resulting in the maintenance of tolerance to self antigens. Ageing is characterized by progressive immunodeficiency, inflammation, and autoimmunity. In this paper we will review the role of DCs in inflammation and autoimmunity in human ageing and will highlight the observations that DCs from aged humans display impairment in their capacity to uptake apoptotic cells, and paradoxically induce proinflammatory response and increased reactivity to self antigen (DNA). DNA from aged is hypomethylated and hypomethylation is associated with increased immunogenecity of self DNA. [ABSTRACT FROM AUTHOR]

Sebaceous adenitis is a non-inflammatory condition characterised by scaling and alopecia. A predisposition is described in some breeds, such as the Standard Poodle and the Akita, but the condition can occur in any breed. The diagnosis is confirmed on histology, by demonstrating the presence of inflammatory cells targeting the sebaceous glands in the early stages of the disorder, or by the total absence of sebaceous glands in the end stage. Several management options are discussed in this paper. [ABSTRACT FROM AUTHOR]

Macropathogens, such as multicellular helminths, are considered masters of immunoregulation due to their ability to escape host defense and establish chronic infections. Molecular crosstalk between the host and the parasite starts immediately after their encounter, which infiuences the course and development of both the innate and adaptive arms of the immune response. Helminths can modulate dendritic cells (DCs) function and induce immunosuppression which is mediated by a regulatory network that includes regulatory T (Treg) cells, regulatory B (Breg) cells, and alternatively activated macrophages (AAMs). In this way, helminths suppress and control both parasite-specific and unrelated immunopathology in the host such as Th1-mediated autoimmune and Th2-mediated allergic diseases. However, certain helminths favour the development or exacerbation of allergic responses. In this paper, the cell types that play an essential role in helminth-induced immunoregulation, the consequences for inflammatory diseases, and the contrasting effects of Toxocara and Trichinella infection on allergic manifestations are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Over the last decades there has been an increasing interest in a possible role of curcumin on cancer. Although curcumin is considered safe for healthy people, conclusive evidence on the safety and efficacy of curcumin for patients with monoclonal gammopathies is, so far, lacking. The present paper reviews the literature on molecular, cellular and clinical effects of curcumin in an attempt to identify, reasons for optimism but also for concern. The results of this critical evaluation can be useful for both patient- selection and monitoring in the context of clinical trials. Curcumin might be helpful for some but certainly not for all patients with monoclonal gammopathies. It is important to avoid unnecessary detrimental side effects in some in order to safeguard curcumin for those that could benefit. Parameters for patient monitoring, that can be used as early warning signs and as indicators of a favorable development have therefore been suggested. [Copyright &y& Elsevier]

Interaction between the nervous and immune systems greatly contributes to inflammatory disease. In organs at the interface between our body and the environment, the sensory neuropeptide substance P (SP) is one key mediator of an acute local stress response through neurogenic inflammation but may also alter cytokine balance and dendritic cell (DC) function. Using a combined murine allergic inflammation/noise stress model with C57BL/6 mice, we show in this paper that SP-released during repeated stress exposure-has the capacity to markedly attenuate inflammation. In particular, repeated stress exposure prior to allergen sensitization increases DC-nerve fiber contacts, enhances DC migration and maturation, alters cytokine balance, and increases levels of IL-2 and T regulatory cell numbers in local lymph nodes and inflamed tissue in a neurokinin 1-SP-receptor (neurokinin-1 receptor)-dependent manner. Concordantly, allergic inflammation is significantly reduced after repeated stress exposure. We conclude that SP/repeated stress prior to immune activation acts protolerogenically and thereby beneficially in inflammation. [ABSTRACT FROM AUTHOR]

Background: Microarray experiments in mice have shown that high fat diet can lead to elevated expression of genes that are disproportionately associated with immune functions. These effects of high fat (atherogenic) diet may be due to infiltration of tissues by leukocytes in coordination with inflammatory processes. Methodology/Principal Findings: The Novartis strain-diet-sex microarray database (GSE10493) was used to evaluate the hepatic effects of high fat diet (4 weeks) in 12 mouse strains and both genders. We develop and apply an algorithm that identifies ''signature transcripts'' for many different leukocyte populations (e.g., T cells, B cells, macrophages) and uses this information to derive an in silico ''inflammation profile''. Inflammation profiles highlighted monocytes, macrophages and dendritic cells as key drivers of gene expression patterns associated with high fat diet in liver. In some strains (e.g., NZB/BINJ, B6), we estimate that 50-60% of transcripts elevated by high fat diet might be due to hepatic infiltration by these cell types. Interestingly, DBA mice appeared to exhibit resistance to localized hepatic inflammation associated with atherogenic diet. A common characteristic of infiltrating cell populations was elevated expression of genes encoding components of the tolllike receptor signaling pathway (e.g., Irf5 and Myd88). Conclusions/Significance: High fat diet promotes infiltration of hepatic tissue by leukocytes, leading to elevated expression of immune-associated transcripts. The intensity of this effect is genetically controlled and sensitive to both strain and gender. The algorithm developed in this paper provides a framework for computational analysis of tissue remodeling processes and can be usefully applied to any in vivo setting in which inflammatory processes play a prominent role. [ABSTRACT FROM AUTHOR]

Chronic inflammation of the adipose tissue (AT) is a critical component of obesity-induced insulin resistance and type 2 diabetes. Adipose tissue immune cells, including AT macrophages (ATMs), AT dendritic cells (ATDCs), and T cells, are dynamically regulated by obesity and participate in obesity-induced inflammation. Among AT resident immune cells, ATDCs are master immune regulators and engage in crosstalk with various immune cells to initiate and regulate immune responses. However, due to confounding markers and lack of animal models, their exact role and contribution to the initiation and maintenance of AT inflammation and insulin resistance have not been clearly elucidated. This paper reviews the current understanding of ATDCs and their role in obesity-induced AT inflammation. We also provide the potential mechanisms by which ATDCs regulate AT inflammation and insulin resistance in obesity. Finally, this review offers perspectives on ways to better dissect the distinct functions and contributions of ATDCs to obesity. [ABSTRACT FROM AUTHOR]

The pulmonary innate immune system is heavily implicated in the perpetual airway inflammation and impaired host defense characterizing Chronic Obstructive Pulmonary Disease (COPD). The airways of patients suffering from COPD are infiltrated by various immune and inflammatory cells including macrophages, neutrophils, T lymphocytes, and dendritic cells. While the role of macrophages, neutrophils and T lymphocytes is well characterized, the contribution of dendritic cells to COPD pathogenesis is still the subject of emerging research. A paper by Botelho and colleagues in the current issue of Respiratory Research investigates the importance of dendritic cell recruitment in cigarette-smoke induced acute and chronic inflammation in mice. Dendritic cells of the healthy lung parenchyma and airways perform an important sentinel function and regulate immune homeostasis. During inflammatory responses the function and migration pattern of these cells is dramatically altered but the underlying mechanisms are incompletely understood. Botelho and colleagues demonstrate here the importance of IL-1R1/IL-1α related mechanisms including CCL20 production in cigarette-smoke induced recruitment of dendritic cells and T cell activation in the mouse lung. [ABSTRACT FROM AUTHOR]

Psoriasis is a common non-communicable chronic immune-mediated skin disease, affecting approximately 125 million people in the world. Its pathogenesis results from a combination of genetic and environmental factors. The pathogenesis of psoriasis seems to be driven by the interaction between innate immune cells, adaptive immune cells and keratinocytes, in a process mediated by cytokines (including interleukins (IL)-6, IL-17 and IL-22, interferon and tumor necrosis factor) and other signaling molecules. This leads to an inflammatory process with increased proliferation of epidermal cells, neo-angiogenesis and infiltration of dendritic cells in the skin. Dysfunctional de novo glucocorticoid synthesis in psoriatic keratinocytes and the skin microbiome have also been suggested as mediators in the pathogenesis of this disease. To understand psoriasis, it is essential to comprehend the processes underlying the skin immunity and neuroendocrinology. This review paper focuses on the skin as a neuroendocrine organ and summarizes what is known about the skin immune system, the brain–skin connection and the role played by the serotonergic system in skin. Subsequently, the alterations of neuroimmune processes and of the serotonergic system in psoriatic skin are discussed, as well as, briefly, the genetic basis of psoriasis. [ABSTRACT FROM AUTHOR]

Inflammatory processes are prominent in various types of human and experimental pulmonary hypertension (PH) and are increasingly recognized as major pathogenic components of pulmonary vascular remodeling. Macrophages, T and B lymphocytes, and dendritic cells are present in the vascular lesions of PH, whether in idiopathic pulmonary arterial hypertension (PAH) or PAH related to more classical forms of inflammatory syndromes such as connective tissue diseases, human immunodeficiency virus (HIV), or other viral etiologies. Similarly, the presence of circulating chemokines and cytokines, viral protein components (e.g., HIV-1 Nef), and increased expression of growth (such as vascular endothelial growth factor and platelet-derived growth factor) and transcriptional (e.g., nuclear factor of activated T cells or NFAT) factors in these patients are thought to contribute directly to further recruitment of inflammatory cells and proliferation of smooth muscle and endothelial cells. Other processes, such as mitochondrial and ion channel dysregulation, seem to convey a state of cellular resistance to apoptosis; this has recently emerged as a necessary event in the pathogenesis of pulmonary vascular remodeling. Thus, the recognition of complex inflammatory disturbances in the vascular remodeling process offers potential specific targets for therapy and has recently led to clinical trials investigating, for example, the use of tyrosine kinase inhibitors. This paper provides an overview of specific inflammatory pathways involving cells, chemokines and cytokines, cellular dysfunctions, growth factors, and viral proteins, highlighting their potential role in pulmonary vascular remodeling and the possibility of future targeted therapy. [Copyright &y& Elsevier]

The article focuses on a research paper investigating whether it is possible to induce antitumor responses in vivo in cancer patients by activating natural killer T (NKT) cells, which are induced to proliferate by dendritic cells. The patients experienced temporary inflammatory symptoms as well as respiratory symptoms in individuals with pulmonary metastases. The study offers clinical evidence that NKT cells can bridge innate and acquired immunity to induce secondary antitumor immune responses.

Summary A heterogeneous mixture of lipids called oxPAPC, derived from dying cells, can hyperactivate dendritic cells (DCs) but not macrophages. Hyperactive DCs are defined by their ability to release interleukin-1 (IL-1) while maintaining cell viability, endowing these cells with potent aptitude to stimulate adaptive immunity. Herein, we found that the bacterial lipopolysaccharide receptor CD14 captured extracellular oxPAPC and delivered these lipids into the cell to promote inflammasome-dependent DC hyperactivation. Notably, we identified two specific components within the oxPAPC mixture that hyperactivated macrophages, allowing these cells to release IL-1 for several days, by a CD14-dependent process. In murine models of sepsis, conditions that promoted cell hyperactivation resulted in inflammation but not lethality. Thus, multiple phagocytes are capable of hyperactivation in response to oxPAPC, with CD14 acting as the earliest regulator in this process, serving to capture and transport these lipids to promote inflammatory cell fate decisions. [ABSTRACT FROM AUTHOR]