Abstract
The adaptive immune system involves antigen-specific host defense mechanisms mediated by T and B cells. In particular, CD4+ T cells play a central role in the elimination of pathogens. Immunological tolerance in the thymus regulates T lymphocytes to avoid self-components, including induction of cell death in immature T cells expressing the self-reactive T-cell receptor repertoire. In the periphery, mature T cells are also regulated by tolerance, e.g., via induction of anergy or regulatory T cells. Thus, T cells strictly control intrinsic signal transduction to prevent excessive responses or self-reactions. If the inhibitory effects of T cells on these mechanisms are disrupted, T cells may incorrectly attack self-components, which can lead to autoimmune disease. The functions of T cells are supported by post-translational modifications, particularly phosphorylation, of signaling molecules, the proper regulation of which is controlled by endogenous mechanisms within the T cells themselves. In recent years, molecular targeted agents against kinases have been developed for treatment of autoimmune diseases. In this review, we discuss T-cell signal transduction in autoimmune disease and provide an overview of acetylation-mediated regulation of T-cell signaling pathways.
Highlights
T cells play an essential role in defending the body against pathogens
Because Tumor necrosis factor-α (TNFα) blocks infectious diseases caused by intracellular pathogens, such as mycobacteria, Pneumocystis carinii, and other fungi [126,127,128,129], and induces tumor cell lysis, its inhibition may result in increased incidence of opportunistic infections and malignancy of cancers
We found that cytoplasmic acetylation plays a role in the negative control of IL-2 receptor (IL-2R) signaling via the Janus Kinase (JAK)/STAT5 pathway [9]
Summary
T cells play an essential role in defending the body against pathogens. CD4+ T cells promote the elimination of infectious agents by activating other types of cells, such as macrophages, whereas CD8+ T cells induce cell death in virus-infected cells [1]. When T cells recognize self-antigens, they may engage inhibitory receptors of the CD28 family, such as cytotoxic T lymphocyte antige-4 (CTLA-4) and programmed death-1 (PD-1) [12,14,15], which function to terminate the T cell response. CTLA-4 delivers inhibitory signals that negate the signals triggered by the TCR Another inhibitory receptor is PD-1 [12,16], which recognizes two ligands, programmed death 1 ligand 1 (PD-L1) and PD-L2, expressed on antigen-presenting cells. This ligand binding leads to suppression of T cells. Dysfunction of T-cell regulatory pathways causes autoimmune disease Both phosphorylation and acetylation are closely involved in T-cell function. We focus on autoimmune responses observed in animal models as well as their corresponding diseases
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