| First Author | Rani L | Year | 2022 |
| Journal | Eur J Immunol | Volume | 52 |
| Issue | 11 | Pages | 1842-1858 |
| PubMed ID | 36074916 | Mgi Jnum | J:340931 |
| Mgi Id | MGI:7435500 | Doi | 10.1002/eji.202149674 |
| Citation | Rani L, et al. (2022) IL-3 regulates the differentiation of pathogenic Th17 cells. Eur J Immunol 52(11):1842-1858 |
| abstractText | 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-alpha(+) , IL-17A(+) IFN-gamma(+) and IL-23R(+) Th17 cells, secretion of GM-CSF and IFN-gamma, 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. |
