regulation of regulatory T cell differentiation

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of differentiation of regulatory T cells. [ISBN:0781735149]

Regulation of regulatory T cell (Treg) differentiation is a complex process involving a tightly coordinated interplay of signaling pathways, transcription factors, and epigenetic modifications. Treg cells are crucial for maintaining immune homeostasis by suppressing excessive immune responses and preventing autoimmunity. Their development from naive CD4+ T cells is initiated by the interaction of the T cell receptor (TCR) with antigen presented by antigen-presenting cells (APCs) in the context of a specific cytokine milieu. The cytokine TGF-β plays a pivotal role in initiating Treg differentiation by inducing the expression of the transcription factor Foxp3, the master regulator of Treg lineage commitment. Foxp3 directly controls the expression of a network of genes that define Treg cell function, including cytotoxic T-lymphocyte antigen 4 (CTLA-4), interleukin-10 (IL-10), and glucocorticoid-induced tumor necrosis factor receptor (GITR). The expression of these genes is further influenced by other transcription factors such as STAT5, RUNX1, and NFAT, which are activated by signaling pathways downstream of TCR and cytokine receptors. The differentiation process is also regulated by epigenetic modifications, including DNA methylation and histone acetylation, which influence the accessibility of regulatory elements in the Foxp3 locus and the expression of Treg-specific genes. The balance of pro- and anti-inflammatory cytokines in the microenvironment further modulates Treg differentiation. IL-2, while initially required for Treg survival and proliferation, can also promote the differentiation of effector T cells in the absence of TGF-β. Conversely, cytokines like IL-6 and IL-21 can inhibit Treg differentiation by interfering with Foxp3 expression and promoting the development of Th17 cells. Furthermore, the differentiation process can be influenced by environmental factors such as gut microbiota composition and exposure to pathogens. The regulation of Treg differentiation is a highly dynamic and context-dependent process that is crucial for maintaining immune tolerance and preventing autoimmunity.'
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Proteins (1)

Compounds (2)