TY - JOUR
T1 - TNF receptor-associated factor (TRAF) signaling network in CD4+ T-Lymphocytes
AU - So, Takanori
AU - Nagashima, Hiroyuki
AU - Ishii, Naoto
N1 - Publisher Copyright:
© 2015 Tohoku University Medical Press.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2015
Y1 - 2015
N2 - CD4+ T helper cells (TH cells), such as TH1, TH2, TH17, TFH, and Treg cells, play critical roles in host defense against infection and in the pathogenesis of immune-mediated diseases. Antigen-presenting cells, such as dendritic cells, deliver three kinds of signals essential for the activation, differentiation, and survival of naïve CD4+ T cells: the first signal is transmitted through T-cell receptors (TCRs) providing the specificity of the immune response and initiating the earliest signals leading to T-cell activation, the second signal through costimulatory receptors promoting the survival and clonal expansion of the antigen-primed T cells, and the third signal through cytokine receptors directing the differentiation of naïve CD4+ T cells into the various TH subsets. Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs), which are composed of six TRAF proteins (TRAF1-TRAF6) with a conserved C-terminal TRAF domain, are intracellular signaling adaptors that mediate the link between receptor-proximal activation events and intracellular signaling proteins. There is growing evidence that TRAFs recruited to TCRs, costimulatory TNFRs, and cytokine receptors play crucial roles in key signaling events in CD4+ T cells and control the lineage commitment, sigfunctionality, and life-and-death decisions of different TH subsets. In this review, we summarize the TRAFs’ physiological functions in T-cell immunity and the molecular mechanisms by which TRAFs regulate the three signals required for the activation, differentiation, and survival of CD4+ T cells and other T-cell subsets.
AB - CD4+ T helper cells (TH cells), such as TH1, TH2, TH17, TFH, and Treg cells, play critical roles in host defense against infection and in the pathogenesis of immune-mediated diseases. Antigen-presenting cells, such as dendritic cells, deliver three kinds of signals essential for the activation, differentiation, and survival of naïve CD4+ T cells: the first signal is transmitted through T-cell receptors (TCRs) providing the specificity of the immune response and initiating the earliest signals leading to T-cell activation, the second signal through costimulatory receptors promoting the survival and clonal expansion of the antigen-primed T cells, and the third signal through cytokine receptors directing the differentiation of naïve CD4+ T cells into the various TH subsets. Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs), which are composed of six TRAF proteins (TRAF1-TRAF6) with a conserved C-terminal TRAF domain, are intracellular signaling adaptors that mediate the link between receptor-proximal activation events and intracellular signaling proteins. There is growing evidence that TRAFs recruited to TCRs, costimulatory TNFRs, and cytokine receptors play crucial roles in key signaling events in CD4+ T cells and control the lineage commitment, sigfunctionality, and life-and-death decisions of different TH subsets. In this review, we summarize the TRAFs’ physiological functions in T-cell immunity and the molecular mechanisms by which TRAFs regulate the three signals required for the activation, differentiation, and survival of CD4+ T cells and other T-cell subsets.
KW - CD4 T cells
KW - Signalosome
KW - T-cell biology
KW - TNFR
KW - TRAF
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U2 - 10.1620/tjem.236.139
DO - 10.1620/tjem.236.139
M3 - Review article
C2 - 26072698
AN - SCOPUS:84935846818
VL - 236
SP - 139
EP - 154
JO - Tohoku Journal of Experimental Medicine
JF - Tohoku Journal of Experimental Medicine
SN - 0040-8727
IS - 2
ER -