Research ArticleT CELLS

Regulatory T cells in skin are uniquely poised to suppress profibrotic immune responses

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Science Immunology  06 Sep 2019:
Vol. 4, Issue 39, eaaw2910
DOI: 10.1126/sciimmunol.aaw2910

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Skin Tregs rely on Gata3 to curb fibrosis

Hyperactive fibroblasts that overproduce extracellular matrix components are a root cause of tissue fibrosis, a shared feature of many chronic inflammatory diseases. Kalekar et al. found that depletion of regulatory T cells (Tregs) in mice resulted in increased skin fibrosis, prompting them to investigate the mechanisms by which skin-resident Tregs normally prevent excess fibroblast activation. RNA sequencing analysis of skin Tregs revealed preferential expression of transcription factors typically associated with TH2 differentiation, including GATA3 and IRF4. Genetic deletion of Gata3 in Tregs resulted in increases in TH2 cytokine production and excessive dermal fibrosis. These findings reveal that GATA3 expression by skin-resident Tregs is an adaptation to the cutaneous microenvironment that enables these specialized Tregs to maintain homeostatic control of fibroblast activity. See the related Focus by Bal and Stadhouders.

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