IL-3 regulates the differentiation of pathogenic Th17 cells.

Autor: Rani L; Bone and Cartilage Research Laboratory, National Centre for Cell Science, Pune, 411007, India., Kumar A; Bone and Cartilage Research Laboratory, National Centre for Cell Science, Pune, 411007, India., Karhade J; Bone and Cartilage Research Laboratory, National Centre for Cell Science, Pune, 411007, India., Pandey G; Bone and Cartilage Research Laboratory, National Centre for Cell Science, Pune, 411007, India., Guha A; Bone and Cartilage Research Laboratory, National Centre for Cell Science, Pune, 411007, India., Mishra GC; Bone and Cartilage Research Laboratory, National Centre for Cell Science, Pune, 411007, India., Wani MR; Bone and Cartilage Research Laboratory, National Centre for Cell Science, Pune, 411007, India.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2022 Nov; Vol. 52 (11), pp. 1842-1858. Date of Electronic Publication: 2022 Sep 26.
DOI: 10.1002/eji.202149674
Abstrakt: 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.
(© 2022 Wiley-VCH GmbH.)
Databáze: MEDLINE
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