Regulatory T cells (Treg cells) control different aspects of immune responses, but how the effector functions of Treg cells are regulated is incompletely understood. Here we identified TNF receptor-associated factor 3 (TRAF3) as a regulator of Treg cell function. Treg cell-specific ablation of TRAF3 impaired CD4 T cell homeostasis, characterized by an increase in the Th1 type of effector/memory...

TRAF3, a critical regulator of B cell survival, was recently recognized as a tumor suppressor gene in B lymphocytes. Specific deletion of TRAF3 from B lymphocytes leads to spontaneous development of marginal zone lymphomas (MZL) or B1 lymphomas in mice. To identify novel oncogenes and tumor suppressive genes involved in malignant transformation of TRAF3-deficient B cells, we performed a microar...

Interleukin 17 (IL-17) plays critical roles in the pathogenesis of various autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE). How the signals triggered by this powerful inflammatory cytokine are controlled to avoid abnormal inflammatory responses is not well understood. In this study, we report that TRAF3 is a receptor proximal negative regulator of IL-17 receptor (...

The Lymphotoxinreceptor (LT R) activates the NFB2 transcription factors, p100 and RelB, by regulating the NFB-inducing kinase (NIK). Constitutive proteosomal degradation of NIK limits NFB activation in unstimulated cells by the ubiquitin:NIK E3 ligase comprised of subunits TNFR-associated factors (TRAF)3, TRAF2 and cellular inhibitor of apoptosis (cIAP). However, the mechanism releasing NIK fro...

Tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3) regulates both innate and adaptive immunity by modulating signaling by Toll-like receptors (TLR) and TNF receptors. TRAF3 was recently identified as a tumor suppressor in human multiple myeloma, suggesting a prominent role in plasma cell homeostasis. We have generated transgenic mice expressing human TRAF3 in lymphocytes. These mi...

Proper activation of nuclear factor (NF)-kappaB transcription factors is critical in regulating fundamental biological processes such as cell survival and proliferation, as well as in inflammatory and immune responses. Recently, the NF-kappaB signaling pathways have been categorized into the canonical pathway, which results in the nuclear translocation of NF-kappaB complexes containing p50, and...

In our Select pages, we highlight exciting themes that emerge from our review of the recent literature. In this issue's Immunology Select, we discuss a cluster of recent papers that further our understanding of the host innate immune response to viruses and provide an example of the evasion of the immune response by a viral protein. The innate immune response is an early line of defense against...

background: toll- like receptors (tlrs) play an important role in the recognition of damps and pamps and induction ofinflammation. previous studies demonstrated that depression and anxiety can influence the expression levels of immune related molecules. our previous study revealed that mrna levels of irak4, traf3 and irf7 were significantly decreased in chronic hbv infected (chb) patients when ...

Tumor necrosis factor receptors (TNFR) are single transmembrane-spanning glycoproteins that bind cytokines and trigger multiple signal transduction pathways. Many of these TNFRs rely on interactions with TRAF proteins that bind to the intracellular domain of the receptors. CD40 is a member of the TNFR family that binds to several different TRAF proteins. We have determined the crystal structure...

TNF receptor-associated factors (TRAFs) are multifunctional adaptor proteins involved in temporal and spatial coordination of signals necessary for normal immune function. Here, we report that TRAF3, a TRAF family member with a key role in Toll-like and TNF family receptor signaling and suppressor of lymphomagenesis, is post-translationally modified by the small ubiquitin-related modifier (SUMO...