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A Treg cell Notch4-GDF15 Axis Licenses Tissue Inflammation in Asthma

ABSTRACT: Elucidating the mechanisms that sustain asthmatic inflammation is critical for precision therapies. We found that IL-6 and STAT3-dependent upregulation of Notch4 on Iung tissue regulatory T (Treg) cells is necessary for allergens and particulate matter pollutants to promote airway inflammation. Notch4 subverted Treg cells into TH2 and TH17 effector T (Teff) cells by Wnt and Hippo pathway-dependent mechanisms. Wnt activation induced GDF15 expression in Treg cells, which activated group 2 innate lymphoid cells (ILC2) to provide a feed-forward mechanism for aggravated inflammation. Notch4, Wnt and Hippo were upregulated on circulating Treg cells of asthmatics as a function of disease severity, in association with reduced Treg cell-mediated suppression. Our studies thus identify Notch4-mediated immune tolerance subversion as a fundamental mechanism that licenses tissue inflammation in asthma.

ORGANISM(S): Mus musculus

PROVIDER: GSE151763 | GEO | 2020/09/01

REPOSITORIES: GEO

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| S-EPMC7578174 | biostudies-literature

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