The severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2) that appeared in December 2019 has precipitated the global pandemic Coronavirus Disease 2019 (COVID-19). However, in many parts of Africa fewer than expected cases of COVID-19, with lower rates of mortality, have been reported. Individual human leukocyte antigen (HLA) alleles can affect both the susceptibility and the severity of viral infections. In the case of COVID-19 such an analysis may contribute to identifying individuals at higher risk of the disease and the epidemiological level to understanding the differences between countries in the epidemic patterns. It is also recognized that first antigen exposure influences the consequence of subsequent exposure. We thus propose a theory incorporating HLA antigens, the “original antigenic sin (OAS)” effect, and presentation of viral peptides which could explain with differential susceptibility or resistance to SARS-CoV-2 infections.

Background: Rheumatoid arthritis ( RA) is a severe inflammatory joint disorder and several studies have taken note of the probability that microRNAs ( miRNAs) play an important role in RA pathogenesis. MiR-146 and miR-155 arose as primary immune response regulators. Mesenchymal stem cells (MSCs) immunomodulatory function is primarily regulated by paracrine factors, such as exosomes. Exosomes, which serve as carriers of genetic information in cell-to-cell communication, transmit miRNAs between cells and have been studied as vehicles for the delivery of therapeutic molecules. Aims : The current research aimed to investigate the therapeutic effect of miR-146a/miR-155 transduced mesenchymal stem cells (MSC)-derived exosomes on the immune response. Methods: Here, exosomes were extracted from normal MSCs with over-expressed miR-146a/miR-155; Splenocytes were isolated from collagen-induced arthritis (CIA) and control mice. Expression levels miR-146a and miR-155 were then monitored. Flow cytometry was performed to assess the impact of the exosomes on regulatory T-cell (Treg) levels. Expression of some key autoimmune response genes and their protein products including retinoic acid-related orphan receptor (ROR)-γt, tumor necrosis factor (TNF)-α, interleukin (IL)-17, -6, -10, and transforming growth factor (TGF)-β in the Splenocytes were determined using both quantitative real-time PCR and ELISA. Results: The results showed that miR-146a was mainly down-regulated in CIA mice. Treatment with MSC-derived exosomes and miR-146a/miR-155-transduced MSC-derived exosomes significantly altered the CIA mice Treg cell levels compared to in control mice. miR-146a-transduced MSC-derived exosomes also increased forkhead box P3 (FoxP3), TGFβ and IL-10 gene expression in the CIA mice; miR-155 further increased the gene expressions of RORγt, IL-17, and IL-6 in these mice. Conclusion: Based on the findings here, Exosomes appears to promote the direct intracellular transfer of miRNAs between cells and to represent a possible therapeutic strategy for RA.the manipulation of MSC-derived exosomes with anti-inflammatory miRNA may increase Treg cell populations and anti-inflammatory cytokines. Ultimately, such modulation may promote the recovery of appropriate T-cell responses in inflammatory situations such as RA.

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Recent studies underline the involvement of microRNAs in cancer development through induction of immune suppression milieu and evolution of drug resistance. The goal of this study was to evaluate the effects of miR-146a on regulatory T cells' frequencies, T-lymphocyte proliferation, and cytokine expression as well as drug resistance in cancer cells. We found that miR-146a was overexpressed in colon cancer HT-29 cells. Peripheral blood mononuclear cells were obtained from healthy donors and were co-cultured with transfected HT-29 cells. Afterward, peripheral blood mononuclear cell proliferation, expression of anti-inflammatory cytokines, and regulatory T cells' frequencies were assayed. Also, drug resistance in transfected HT-29 cells was analyzed following treatment with 5-fluorouracil and irinotecan. Overexpression of miR-146a increased transforming growth factor-β and interleukin-10 expressions and enhanced regulatory T cells' frequencies in peripheral blood mononuclear cells. Also, the number of cells undergoing cell cycle arrest and apoptosis significantly decreased in transfected HT-29 cancer cells. In conclusion, upregulation of miR-146a plays an important role in enhancing immune suppression through increasing the regulatory T cells' population. Also, our data indicated that colon cancer drug resistance is possibly associated with miR-146a overexpression.

Regulatory T (Treg) cells take part in immune homeostasis and play a pivotal role in maintaining peripheral tolerance. The aim of this study was to evaluate the frequency and function of Treg cells in active and untreated ulcerative colitis (UC) patients. Thirty-two subjects with newly diagnosed UC and 31 age-matched healthy controls were included in this survey. The frequency of Tregs was analyzed with flow cytometry using CD4, CD25, CD127 and FoxP3 markers. We used surface expression of CD4(+), CD25(+) and CD127(low) markers for isolation of a relatively pure Treg population. Suppressive activity of Tregs was determined by measuring their ability to inhibit the proliferation of T responder cells. UC patients had a lower frequency of CD4(+) CD25(+) CD127(low) FoxP3(+) Treg cells. Additionally, Treg cell-mediated suppression was lower in UC patients compared to controls. The frequency and suppressive capacity of Tregs and MFI of FoxP3 were inversely correlated with disease activity. These results suggest that CD4(+) CD25(+) CD127(low) FoxP3(+) Treg cells may contribute to immunopathogenesis of UC, and assessment of Treg cell frequency and function may have clinical value.

Regulatory T (Treg) cells are essential for maintenance of peripheral tolerance and prevention of autoimmune diseases in part by producing immunosuppressive cytokines. Recently, microRNAs (miRNAs) have also been involved in autoimmune disorders, not least for their crucial role in the regulation of Treg biology and function. We simultaneously investigated the concentration of IL-35, IL-10, TGF-β, and sCD25 in supernatant of cell culture and the expression patterns of several miRNAs in CD4(+)CD25(+) CD127(-/low) FoxP3(+) Tregs of ulcerative colitis (UC) patients. Significantly lower levels of IL-10 and IL-35 were observed in Treg cultures of UC patients. miR-21, miR-146a, and miR-155 levels were downregulated and miR-31 level was upregulated in Tregs of patients. Our results suggest that microRNAs may serve as a novel regulator in function and homoeostasis of UC Treg cells, providing a key role for them in pathophysiology of UC.

Exosomes are small extracellular vesicles that pass genetic material between various cells to modulate or alter their biological function. The role of exosomes is to communicate with the target cell for cell-to-cell communication. Their inherent characteristics of exosomes, such as adhesion molecules, allow targeting specifically to the receiving cell. Exosomes are involved in cell to cell communication in the immune system including antigen presentation, natural killer cells (NK cells) and T cell activation/polarisation, immune suppression and various anti-inflammatory processes. In this review, we have described various functions of exosomes secreted by the immune cells in initiating, activating and modulating immune responses; and highlight the distinct roles of exosomal surface proteins and exosomal cargo. Potential applications of exosomes such as distribution vehicles for immunotherapy are also discussed.

Sepsis is a life-threatening disorder that is caused by a dysregulated inflammatoryresponse during an infection. The disease mostly affects pregnant women, newborns, and patients in intensive care units (ICU). Sepsis treatment is a significant part of a country's health budgets. Delay in the therapy causes irreversible failure of various organs due to the lack of blood supply and reduction of oxygen in the tissues and eventually increased mortality. The involvement of four or five organs by sepsis has been attributed to an increased risk of death to over 90%. Although antibiotics are at the first line of sepsis treatment, they do not possess enough potency to control the disease and prevent subsequent organ failure. The immunomodulatory, anti-inflammatory, anti-apoptotic, and anti-microbial properties of mesenchymal stem cells (MSCs) have been reported in various studies. Therefore, theapplication of MSCs has been considered as a potentially promising therapeutic strategy. In preclinical studies, the administration of MSCs has been associated with reduced bacterial load anddecreased levels of pro-inflammatory factorsas well as the improved function of the different vital organs, including heart, kidney, liver, and lungs. The current study provides a brief review of sepsis and itspathophysiology, and then highlights recent findings in the therapeutic effects of MSCs and MSC-derived secretomein improving sepsis-induced organCopyright © 2020 by the Shock Society. Unauthorized reproduction of this article is prohibited.dysfunction.Besides,eligible sepsis candidates for MSC-therapy and the latest clinical findings in these areashave been reviewed.