Roles of TRAF3 in T cells: many surprises.
Tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) is broadly involved in different receptor-mediated signaling pathways. Considerable progress was made recently in understanding the role of TRAF3 in T cell biology. Here we review these new findings about how TRAF3 participates in T cell development and function. The different roles of TRAF3 in distinct immune cells are also compared. That TRAF3 is required for T cell effector functions, and invariant Natural Killer T cell function and development, was unexpected. Another surprising finding is that TRAF3 normally restrains regulatory T cell development. It is now clear that TRAF3 regulates signaling to T cells not only through costimulatory members of the TNFR superfamily, but also through the T cell receptor complex, and cytokine receptors. The diverse roles it plays support the multifaceted nature of this molecule. How TRAF3 mediates integration of different signaling cascades is an important topic for future study.
a Departments of Microbiology ; University of Iowa ; Iowa City , IA USA.
Zuoan
Z
Yi
Alicia M
AM
Wallis
Gail A
GA
Bishop
D000818:Animals; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D048008:TNF Receptor-Associated Factor 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D015375:Receptors, Interleukin-2; D048008:TNF Receptor-Associated Factor 3
DC, dendritic cell; IBD, inflammatory bowel disease; ICOS, inducible co-stimulator; IKK, IκB kinase; IL-2 receptor; IL-2, interleukin-2; Jak1, Janus kinase 1; LMC, litter mate control; LMP1, latent membrane protein-1; MAPK, mitogen-activated protein kinase; MΦ, macrophage; NIK, NF-κB inducing kinase; NLR, nucleotide binding-oligomerization domain (NOD)-like receptor; RLR, retinoic acid-inducible gene (RIG)-I-like receptor; SLAM, signaling lymphocyte activation molecule; SOCS1, Suppressor of cytokine signaling 1; T cell; T cell receptor; T-TRAF3−/−, CD4CreTRAF3flox/flox; TCPTP, T cell protein tyrosine phosphatase; TCR, T cell receptor; TFH, follicular helper T cell; TFR, follicular Treg cell; TLR, Toll-like receptor; TNFR, Tumor necrosis factor receptor; TRAF3; TRAF3, TNFR-associated factor 3; Tcm cell, central memory T cell; Tem cell, effector memory T cell; Treg cell, regulatory T cell; adaptor molecule; iNKT cell, invariant Natural Killer T cell; invariant Natural Killer T cell; regulatory T cell; signaling pathway