IL-33 activates mTORC1 and modulates glycolytic metabolism in CD8+ T cells

Yuejin Liang, Xiaofang Wang, Hui Wang, Wenjing Yang, Panpan Yi, Lynn Soong, Yingzi Cong, Jiyang Cai, Xuegong Fan, Jiaren Sun

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Interleukin (IL)-33, a member in the IL-1 family, plays a central role in innate and adaptive immunity; however, how IL-33 mediates cytotoxic T-cell regulation and the downstream signals remain elusive. In this study, we found increased mouse IL-33 expression in CD8+ T cells following cell activation via anti-CD3/CD28 stimulation in vitro or lymphocytic choriomeningitis virus (LCMV) infection in vivo. Our cell adoptive transfer experiment demonstrated that extracellular, but not nuclear, IL-33 contributed to the activation and proliferation of CD8+, but not CD4+ T effector cells in LCMV infection. Importantly, IL-33 induced mTORC1 activation in CD8+ T cells as evidenced by increased phosphorylated S6 ribosomal protein (p-S6) levels both in vitro and in vivo. Meanwhile, this IL-33-induced CD8+ T-cell activation was suppressed by mTORC1 inhibitors. Furthermore, IL-33 elevated glucose uptake and lactate production in CD8+ T cells in both dose- and time-dependent manners. The results of glycolytic rate assay demonstrated the increased glycolytic capacity of IL-33-treated CD8+ T cells compared with that of control cells. Our mechanistic study further revealed the capacity of IL-33 in promoting the expression of glucose transporter 1 (Glut1) and glycolytic enzymes via mTORC1, leading to accelerated aerobic glucose metabolism Warburg effect and increased effector T-cell activation. Together, our data provide new insights into IL-33-mediated regulation of CD8+ T cells, which might be beneficial for therapeutic strategies of inflammatory and infectious diseases in the future.

Original languageEnglish (US)
Pages (from-to)61-73
Number of pages13
JournalImmunology
Volume165
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • CD8
  • Glut1
  • IL-33
  • T cells
  • glycolytic metabolism
  • mTORC1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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