title: TNF Receptor-Associated Factor (TRAF) Signaling Network in CD4(+) T-Lymphocytes.
abstract: 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, functionality, 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.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine.
authors.forename: Takanori
authors.initials: T
authors.lastname: So
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagashima
authors.forename: Naoto
authors.initials: N
authors.lastname: Ishii
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor