IL-6 enhances CD4 cell motility by sustaining mitochondrial Ca2+ through the noncanonical STAT3 pathway

Felipe Valença-Pereira, Qian Fang, Isabelle J. Marié, Emily L. Giddings, Karen A. Fortner, Rui Yang, Alejandro V. Villarino, Yina H. Huang, David A. Frank, Haitao Wen, David E. Levy, Mercedes Rincon

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin 6 (IL-6) is known to regulate the CD4 T cell function by inducing gene expression of a number of cytokines through activation of Stat3 transcription factor. Here, we reveal that IL-6 strengthens the mechanics of CD4 T cells. The presence of IL-6 during activation of mouse and human CD4 T cells enhances their motility (random walk and exploratory spread), resulting in an increase in travel distance and higher velocity. This is an intrinsic effect of IL-6 on CD4 T-cell fitness that involves an increase in mitochondrial Ca2+. Although Stat3 transcriptional activity is dispensable for this process, IL-6 uses mitochondrial Stat3 to enhance mitochondrial Ca2+-mediated motility of CD4 T cells. Thus, through a noncanonical pathway, IL-6 can improve competitive fitness of CD4 T cells by facilitating cell motility. These results could lead to alternative therapeutic strategies for inflammatory diseases in which IL-6 plays a pathogenic role.

Original languageEnglish (US)
Article numbere2103444118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number37
DOIs
StatePublished - Sep 14 2021

Keywords

  • CD4 T cells
  • Interleukin-6
  • Mitochondrial calcium
  • Motility
  • STAT3

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'IL-6 enhances CD4 cell motility by sustaining mitochondrial Ca2+ through the noncanonical STAT3 pathway'. Together they form a unique fingerprint.

Cite this