| First Author | Harb H | Year | 2020 |
| Journal | Nat Immunol | Volume | 21 |
| Issue | 11 | Pages | 1359-1370 |
| PubMed ID | 32929274 | Mgi Jnum | J:305853 |
| Mgi Id | MGI:6706600 | Doi | 10.1038/s41590-020-0777-3 |
| Citation | Harb H, et al. (2020) A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma. Nat Immunol 21(11):1359-1370 |
| abstractText | Elucidating the mechanisms that sustain asthmatic inflammation is critical for precision therapies. We found that interleukin-6- and STAT3 transcription factor-dependent upregulation of Notch4 receptor on lung tissue regulatory T (Treg) cells is necessary for allergens and particulate matter pollutants to promote airway inflammation. Notch4 subverted Treg cells into the type 2 and type 17 helper (TH2 and TH17) effector T cells by Wnt and Hippo pathway-dependent mechanisms. Wnt activation induced growth and differentiation factor 15 expression in Treg cells, which activated group 2 innate lymphoid cells to provide a feed-forward mechanism for aggravated inflammation. Notch4, Wnt and Hippo were upregulated in circulating Treg cells of individuals with asthma 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. |
