TRAF2 regulates T cell immunity by maintaining a Tpl2-ERK survival signaling axis in effector and memory CD8 T cells

Xiaoping Xie, Lele Zhu, Zuliang Jie, Yanchuan Li, Meidi Gu, Xiaofei Zhou, Hui Wang, Jae Hoon Chang, Chun Jung Ko, Xuhong Cheng, Shao Cong Sun

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Generation and maintenance of antigen-specific effector and memory T cells are central events in immune responses against infections. We show that TNF receptor-associated factor 2 (TRAF2) maintains a survival signaling axis in effector and memory CD8 T cells required for immune responses against infections. This signaling axis involves activation of Tpl2 and its downstream kinase ERK by NF-κB-inducing kinase (NIK) and degradation of the proapoptotic factor Bim. NIK mediates Tpl2 activation by stimulating the phosphorylation and degradation of the Tpl2 inhibitor p105. Interestingly, while NIK is required for Tpl2-ERK signaling under normal conditions, uncontrolled NIK activation due to loss of its negative regulator, TRAF2, causes constitutive degradation of p105 and Tpl2, leading to severe defects in ERK activation and effector/memory CD8 T cell survival. Thus, TRAF2 controls a previously unappreciated signaling axis mediating effector/memory CD8 T cell survival and protective immunity.

Original languageEnglish (US)
Pages (from-to)2262-2274
Number of pages13
JournalCellular and Molecular Immunology
Volume18
Issue number9
DOIs
StatePublished - Sep 2021

Keywords

  • Bacterial infection
  • Effector and memory CD8 T cells
  • NIK
  • Protective immunity
  • T cell survival
  • TRAF2
  • Tpl2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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