IL-3 regulates the differentiation of pathogenic Th17 cells

Eur J Immunol. 2022 Nov;52(11):1842-1858. doi: 10.1002/eji.202149674. Epub 2022 Sep 26.


IL-17-producing Th17 cells play an important role in pathogenesis of rheumatoid arthritis (RA). Aberrant immune activation due to an imbalance between Th17 and regulatory T (Treg) cells is associated with the development of RA and other autoimmune diseases. Targeting pathogenic Th17 cells and their associated molecules is emerging as a promising strategy to treat and reverse RA. Here, we demonstrate that IL-3 inhibits the differentiation of Th17 cells and promotes the development of Treg cells in IL-2-dependent manner. In IL-2 KO mice, we observed that IL-3 has no effect on differentiation of both Th17 and Treg cells. In addition, IL-3 decreases pathogenic IL-17A+ TNF-α+ , IL-17A+ IFN-γ+ and IL-23R+ Th17 cells, secretion of GM-CSF and IFN-γ, and osteoclastogenesis when presented in the culture together with Th17 polarizing cytokines. Mechanistically, IL-3 regulates the development of Th17 cells through the inhibition of STAT3 phosphorylation. IL-3 treatment significantly decreases the pathogenic Th17 cell responses and arthritic scores in the mouse model of RA. Importantly, IL-3 inhibits the differentiation of human Th17 cells. Thus, our results suggest a novel therapeutic role of IL-3 in the regulation of Th17 cell-mediated pathophysiology of RA.

Keywords: IL-3; Th17; Treg; pathogenicity; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid*
  • Cell Differentiation*
  • Humans
  • Interleukin-17 / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-3* / metabolism
  • Mice
  • T-Lymphocytes, Regulatory / cytology
  • Th17 Cells* / cytology


  • Interleukin-17
  • Interleukin-2
  • Interleukin-3