Rani, L and Kumar , A and Karhade, J and Pandey , G and Guha, A and Mishra, GC and Wani, MR (2022) IL-3 regulates the differentiation of pathogenic Th17 cells. European Journal of Immunololgy..

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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.

Item Type:	Article
Additional Information:	National Centre for Cell Science, Pune, 411007 India
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	21 Oct 2022 07:18
Last Modified:	21 Oct 2022 07:18
URI:	http://nccs.sciencecentral.in/id/eprint/1212

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