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Paper Reading 01 JEM This study is about the regulatory role of Tregs in humoral immune responses. As all we know, B cell is the key mediator of the humoral immunoreaction. Recent studies had reported that Tfrs play an important role in control the GC formation and B cell development. Many previous studies had shown the regulatory function of Tregs in immune response, but the precise mechanisms behind these phenotypes remain unclear. In this paper, the authors pay their attention to explore the role of TRAF3 in the Tregs. Firstly, they construct the Treg cell–specific TRAF3 KO mice . Then they detected the immune homeostasis of the TRAF3 CKO mice and results showed that Treg cell–specific TRAF3 deficiency does not compromise the homeostasis or in vitro function of Treg cells but partially impairs the in vivo functions of Treg cells. They further examined the e homeostasis of CD4+ T cells in peripheral lymphoid organs under nontransferred conditions and found that TRAF3 regulates a specific function, instead of mediating the core suppressive activity, of Treg cells. They also detected the role of Tregs in modulating immune responses to foreign antigens and confirmed that Treg cell–specific TRAF3 regulates antigen-stimulated humoral immune responses. Next, they examined the function of TFH cells and GC formation in vivo. Results demonstrated that Treg cell–specific TRAF3 regulates TFH cell function and GC formation. Finally, they confirmed that TRAF3 deficency in Tregs downregulates ICOS expression in Tregs via a MAP kinase pathway and ICOS is a key regulator for TFR generation. This paper showed a new insight for the TRAF3 in the regulation of Treg cell function and gave us a new understanding about the signaling mechanism regulating the specific functions of Treg cells. http:///10.1084/jem.20131019 02 c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ regulatory T cells Nature communications CD4 T helper (TH) lymphocytes are essential regulators of immune responses and inflammatory diseases. After being activated by professional antigen-presenting cells (APCs), TH cells differentiate into effector cells specialized in cytokine secretion and function. Effector TH cells have been classified as type 1 (TH1), type 2 (TH2), TH17 and Tregs based on their cytokine expression profiles and immune regulatory function. Subsets of CD4+ helper T cells, including TH1, TH2 and TH17 cells, are critical for the eradication of specific pathogens, but if they are uncontrolled, they can contribute to immunopathology, either during infection or during immune system–mediated diseases. There are different mechanisms that keep the homeostasis of immune system including production of the anti-inflammatory cytokine IL-10 and CD4+ regulatory T cells (Treg cells). Many TFs have been shown to modulate IL-10 expression, including c-Maf and although c-Maf has been shown to positively regulate IL-10 expression in vitro, its effects on IL-10 and global gene expression across different immune responses in vivo are unknown. In this paper, the author study the regulatory role of c-Maf in CD4 T cells in vivo. Firstly ,they check the expression of Maf and that of IL-10 correlate in all helper T cell and Treg cell subsets. Results showed that c-Maf might function as a common regulator of IL-10 in CD4+ T cells regardless of the T cell subset. Then they detected the role of c-Maf in different disease model and demonstrated that c-Maf deficiency in CD4+ T cells affects susceptibility to disease in a context-specific manner. To better understand the disease-specific effects of the deletion of c- Maf, they performed RNA-seq analysis of purified CD4+ T cells isolated from different organs in different disease models. Results showed that in addition to controlling TH1 and TH2 responses, c-Maf served a previously unknown, more dominant role in the EAE model, beyond IL-10 expression, by regulating the balance of TH17 cell responses (Rorc) and Foxp3+ Treg cell responses. To identify the molecular mechanisms whereby c-Maf affects gene regulation in CD4+ T cells in vivo, the author used the assay for transposase-accessible chromatin plus sequencing (ATAC-seq) to reveal functionally active genomic regions. Further study showed that IL-2 is a c-Maf target. The decreased expression of Rorc observed in Maf-deficient TH17 cells was caused indirectly via the action of IL-2, since this effect was abolished by neutralization of IL-2. This paper demonstrated a broad yet context specific role for c-Maf in regulating gene expression that allows each type of T cell effector immune response to occur in a controlled yet effective manner and suggested new potential drug target for different disease. https://www./articles/s41590-018-0083-5.pdf END |
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