IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner

Sci Rep. 2016 Nov 4:6:36002. doi: 10.1038/srep36002.


IL-25, a new member of the IL-17 cytokine family, is involved in type 2 immunity initiation and has been associated with the pathogenesis of rheumatoid arthritis (RA). However, its exact role remains unclear. Here, we aimed to analyse IL-25 expression in the serum and synovial fluid of RA patients and evaluated the correlations between serum IL-25 levels, clinical and laboratory values and inflammation cytokines. Additionally, we investigated whether IL-25 can suppress Th1/Th17 responses involved in RA pathogenesis. We further determined whether IL-25 can alleviate collagen-induced arthritis (CIA) development in mice and the underlying mechanisms using in vitro and in vivo experiments. Our results showed that IL-25 was upregulated in the serum and synovial fluid of RA patients. Increased serum IL-25 levels were associated with disease severity and inflammatory response in RA patients. Furthermore, IL-25 inhibited CD4+ T-cell activation and differentiation into Th17 cells, without affecting Th1 cells in human RA and CIA models. Administration of IL-25 could attenuate CIA development by Th17 suppression in an IL-13-dependent manner. Our findings indicate that IL-25 plays a potent immunosuppressive role in the pathogenesis of RA and CIA by downregulating Th17 cell response, and thus, may be a potential therapeutic agent for RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / prevention & control
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Case-Control Studies
  • Cell Differentiation
  • Female
  • Humans
  • Immune Tolerance
  • Interleukin-13 / immunology*
  • Interleukin-17 / blood
  • Interleukin-17 / immunology*
  • Interleukins / immunology
  • Interleukins / therapeutic use
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred DBA
  • Synovial Fluid / immunology
  • Th1 Cells / immunology
  • Th1 Cells / pathology
  • Th17 Cells / immunology*
  • Th17 Cells / pathology


  • IL13 protein, human
  • IL25 protein, human
  • Interleukin-13
  • Interleukin-17
  • Interleukins
  • Mydgf protein, mouse