IL‐3 regulates the differentiation of pathogenic Th17 cells
Lekha Rani, Anil Kumar, Juilee Karhade, Garima Pandey, Adrita Guha, Gyan C. Mishra, Mohan R. Wani
Abstract
Abstract 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.