| First Author | Laky K | Year | 2023 |
| Journal | Sci Immunol | Volume | 8 |
| Issue | 79 | Pages | eabp9940 |
| PubMed ID | 36608150 | Mgi Jnum | J:338986 |
| Mgi Id | MGI:7517261 | Doi | 10.1126/sciimmunol.abp9940 |
| Citation | Laky K, et al. (2023) Epithelial-intrinsic defects in TGFbetaR signaling drive local allergic inflammation manifesting as eosinophilic esophagitis. Sci Immunol 8(79):eabp9940 |
| abstractText | Allergic diseases are a global health challenge. Individuals harboring loss-of-function variants in transforming growth factor-beta receptor (TGFbetaR) genes have an increased prevalence of allergic disorders, including eosinophilic esophagitis. Allergic diseases typically localize to mucosal barriers, implicating epithelial dysfunction as a cardinal feature of allergic disease. Here, we describe an essential role for TGFbeta in the control of tissue-specific immune homeostasis that provides mechanistic insight into these clinical associations. Mice expressing a TGFbetaR1 loss-of-function variant identified in atopic patients spontaneously develop disease that clinically, immunologically, histologically, and transcriptionally recapitulates eosinophilic esophagitis. In vivo and in vitro, TGFbetaR1 variant-expressing epithelial cells are hyperproliferative, fail to differentiate properly, and overexpress innate proinflammatory mediators, which persist in the absence of lymphocytes or external allergens. Together, our results support the concept that TGFbeta plays a fundamental, nonredundant, epithelial cell-intrinsic role in controlling tissue-specific allergic inflammation that is independent of its role in adaptive immunity. |
