Role of tumor necrosis factor receptor-associated factor 5 in B-and T-lymphocytes

Mari Hikosaka Kuniishi, Naoto Ishii, Takanori So*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are a family of intracellular signaling adaptors that associate with the cytoplasmic tails of a diverse range of lymphocyte receptors, including members of the TNFR superfamily, the Toll-like receptor (TLR)/interleukin-1 (IL-1) receptor superfamily, and the IL-6 receptor family that are major targets for therapeutic intervention for inflammatory diseases. TRAF5 is one of the seven family members of the TRAF family and is highly expressed by B-and T-lymphocytes. As compared to other family members, the biological and pathophysiological functions of TRAF5 have remained ambiguous since its discovery. TRAF5 promotes lymphocyte signaling for the TNFR family molecules such as glucocorticoid-induced TNFR family-related protein (GITR), CD27, and CD40. In contrast, TRAF5 limits the activity of the common signaling receptor subunit glycoprotein 130 kDa (gp130) in CD4+ T cells that requires signaling by IL-6 and IL-27. TRAF5 also restrains TLR signaling in B cells. Thus, TRAF5 regulates lymphocyte signaling in both positive and negative ways. This review will summarize the findings of recent studies of TRAF5 in terms of how TRAF5 regulates signaling in lymphocytes and other cell types and how TRAF5 expression contributes to inflammatory and autoimmune diseases in mice and humans.

Original languageEnglish
Pages (from-to)40-55
Number of pages16
JournalExploration of Immunology
Volume3
Issue number1
DOIs
StatePublished - 2023

Keywords

  • Janus kinase
  • Toll-like receptor
  • Tumor necrosis factor receptor-associated factor 5
  • autoimmunity
  • inflammation
  • interleukin-6
  • signal transducer and activator of transcription
  • tumor necrosis factor receptor superfamily

ASJC Scopus subject areas

  • Immunology and Microbiology (miscellaneous)
  • Immunology
  • Microbiology

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