The immunological significance of tumor necrosis factor receptor-associated factors (TRAFs).

Takanori So

International immunology 2022 Jan 01

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The tumor necrosis factor receptor (TNFR)-associated factor (TRAF) family of molecules are intracellular signaling adaptors and control diverse signaling pathways mediated not only by the TNFR superfamily and the Toll-like receptor/IL-1 receptor superfamily but also by unconventional cytokine receptors such as IL-6 and IL-17 receptors. There are seven family members, TRAF1 to TRAF7, in mammals. Exaggerated immune responses induced through TRAF signaling downstream of these receptors often lead to inflammatory and autoimmune diseases including rheumatoid arthritis, inflammatory bowel disease, psoriasis and autoinflammatory syndromes, and thus those signals are major targets for therapeutic intervention. For this reason, it has been very important to understand signaling mechanisms regulated by TRAFs that greatly impact on life/death decisions and the activation, differentiation and survival of cells of the innate and adaptive immune systems. Accumulating evidence suggests that dysregulated cellular expression and/or signaling of TRAFs causes overproduction of pro-inflammatory cytokines, which facilitates aberrant activation of immune cells. In this review, I will explain the structural and functional aspects that are responsible for the cellular activity and disease outcomes of TRAFs, and summarize the findings of recent studies on TRAFs in terms of how individual TRAF family molecules regulate biological and disease processes in the body in both positive and negative ways. This review also discusses how TRAF mutations contribute to human disease. © The Japanese Society for Immunology. 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Takanori So. The immunological significance of tumor necrosis factor receptor-associated factors (TRAFs). International immunology. 2022 Jan 01;34(1):7-20