In particular, T17 cells have been reported to play a central role in the pathogenesis of psoriasis, in which IL-17 secreted by T17 cells in the skin promotes keratinocyte hyperproliferation and the recruitment of neutrophils [13]

In particular, T17 cells have been reported to play a central role in the pathogenesis of psoriasis, in which IL-17 secreted by T17 cells in the skin promotes keratinocyte hyperproliferation and the recruitment of neutrophils [13]. lymphocytes (T cells) that develop in the thymus. T cells are classified into two types, T cells and T cells [1]. These different T cell lineages express different types of T cell antigen receptors (TCRs), i.e., TCR or TCR, that are composed of different sets of somatically rearranged TCR chains and CD3 subunits. The development and function of T cells depend on the TCR recognition of antigen peptides presented by the major histocompatibility complex (MHC) proteins. Upon the recognition of the peptide-MHC (pMHC) complex, T cells differentiate into effector cells that exert cytotoxic activity or produce cytokines so as to activate innate immune cells or B cells, thus protecting against invading pathogens and tumors [2]. In contrast, no coherent mechanism exists for antigen recognition by T cells. The TCR reportedly recognizes structurally diverse and biologically unrelated compounds such as lipopeptides, microorganism-derived proteins, and self-proteins. The self-proteins include stress-associated proteins and non-classical MHC [3, 4] as well as classical pMHC complexes [5]. Thus, the antigen recognition mode and differentiation requirements of T cells are different from those of T cells. In certain infections, T cells, which have the inherent ability to produce cytokines such as interferon- (IFN) and interleukin-17 (IL-17), contribute to rapid immune responses against a broad spectrum of pathogens and also the smooth transition from the innate to adaptive immune response [4, 6]. Recent studies have demonstrated that IL-17-producing T (T17) cells have an anti-bacterial ability, but also homeostatic capacity under certain physiological conditions. In the bone fracture repair process, T17 cells promote bone regeneration by accelerating osteoblast differentiation [7]. A recent study showed that T17 cells in adipose tissue control thermogenesis in response to cold temperature [8]. However, T17 cells are also notorious for their ability to induce inflammatory diseases, autoimmunity, and metastasis in mice and humans [9C12]. In particular, T17 cells have been reported to play a central role in the pathogenesis of psoriasis, in which IL-17 secreted by T17 cells in the skin promotes keratinocyte hyperproliferation and the recruitment of neutrophils [13]. A recent report by Prinz and co-workers demonstrated the non-redundant function of T17 cells for psoriasis-like dermatitis using a newly generated mouse strain that enables drug-inducible depletion of T cells [14]. Although Mecarbinate considerable attention has been paid to the pathophysiological function of proinflammatory T cells, it has remained largely unclear how effector T cells are generated. Unlike T cells, in which effector differentiation occurs in the periphery, both the T17- and IFN-producing T (T1) cells are induced during development in the thymus [15]. In the mouse, T cells can be sub-classed based on the usage of the TCR variable region (V), and the generation of those T cell subsets is developmentally regulated during ontogeny: V5 cells develop during the fetal period, V6 cells around birth, V4 cells in the neonatal period, and V1 Mecarbinate and V7 cells at adult stage. There is also a close linkage between the V subset and effector function: V4 or V6 cells preferentially include T17, while the majority of V1, V5 and V7 cells differentiate into T1 [4]. These Mecarbinate distinct T cell subsets are distributed in GPATC3 lymphoid as well as mucosal tissues. In this review, we will discuss the current knowledge of the molecular mechanism of TCR signal transduction and its role in the thymic development of proinflammatory T cells. Overview of TCR signaling The TCR is a complex receptor that consists of receptor subunits (TCR or ) Mecarbinate and CD3 subunits (CD3, , , and ) [16]. TCR signal transduction involves the conformational change, as well as the recruitment and phosphorylation of multiple proteins, including CD3 subunits, kinases, phosphatases, and adaptor proteins (Fig.?1). Among them, most of the kinases act as a driver of TCR signaling. Zap70, a member of the Syk family kinases, plays a key role in TCR signal.

Comments are closed.