IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner

J Biol Chem. 2007 Nov 30;282(48):34605-10. doi: 10.1074/jbc.M705100200. Epub 2007 Sep 20.

Abstract

CD4(+) helper T cells can differentiate into several possible fates including: Th1, Th2, T regulatory, and Th17 cells. Although, cytokine production by non-T cells is an important factor in helper T cell differentiation, a characteristic feature of both Th1 and Th2 lineages is their ability to secrete cytokines that promote their respective differentiation. However, cytokines produced by T cells that help to sustain Th17 cells have not yet been identified. Here we show that IL-21 is a product of Th17 cells, which is induced in a Stat3-dependent manner. Additionally, Stat3 can directly bind the Il21 promoter. IL-21 also induces IL-17 production and expression of the transcription factor, RORgammat. Furthermore, generation of Th17 cells in the conventional manner is attenuated by blocking IL-21. IL-21 is known to activate Stat3 and its ability to induce Th17 differentiation is abrogated in the absence of Stat3. These data argue that IL-21 serves as an autocrine factor secreted by Th17 cells that promotes or sustains Th17 lineage commitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cytokines / metabolism
  • Gene Expression Regulation*
  • Interleukin-17 / biosynthesis*
  • Interleukins / biosynthesis*
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / metabolism
  • STAT3 Transcription Factor / biosynthesis*
  • STAT3 Transcription Factor / genetics
  • Spleen / cytology
  • T-Lymphocytes / metabolism*

Substances

  • Cytokines
  • Interleukin-17
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • interleukin-21