Role of IL-6 in the commitment of T cell subsets

Cytokine. 2021 Oct;146:155654. doi: 10.1016/j.cyto.2021.155654. Epub 2021 Jul 26.


IL-6 gained much attention with the discovery that this cytokine is a non-redundant differentiation factor for Th17 cells and T follicular helper cells. Adaptive immune responses to fungi and extracellular bacteria are impaired in the absence of IL-6. IL-6 is also required for the induction of ROR-γt+ Treg cells, which are gatekeepers of homeostasis in the gut lamina propria in the presence of commensal bacteria. Conversely, severe immunopathology in T cell-mediated autoimmunity is mediated by Th17 cells that rely on IL-6 for their generation and maintenance. Recently, it has been discovered that the differentiation of these distinct T helper cell subsets may be linked to distinct signaling modalities of IL-6. Here, we summarize the current knowledge on the mode of action of IL-6 in the differentiation and maintenance of T cell subsets and propose that a context-dependent understanding of the impact of IL-6 on T cell subsets might inform rational IL-6-directed interventions in autoimmunity and chronic inflammation.

Keywords: Autoimmunity; Host defence; IL-6; IL-6 cluster signaling; T follicular helper cell; Th17 cell; Treg cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmunity
  • Cell Lineage*
  • Humans
  • Interleukin-6 / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology*


  • Interleukin-6