| First Author | Schmitt P | Year | 2024 |
| Journal | J Exp Med | Volume | 221 |
| Issue | 6 | PubMed ID | 38597952 |
| Mgi Jnum | J:358507 | Mgi Id | MGI:7623093 |
| Doi | 10.1084/jem.20231236 | Citation | Schmitt P, et al. (2024) TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation. J Exp Med 221(6) |
| abstractText | Epithelium-derived cytokines or alarmins, such as interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), are major players in type 2 immunity and asthma. Here, we demonstrate that TNF-like ligand 1A (TL1A) is an epithelial alarmin, constitutively expressed in alveolar epithelium at steady state in both mice and humans, which cooperates with IL-33 for early induction of IL-9high ILC2s during the initiation of allergic airway inflammation. Upon synergistic activation by IL-33 and TL1A, lung ILC2s acquire a transient IL-9highGATA3low "ILC9" phenotype and produce prodigious amounts of IL-9. A combination of large-scale proteomic analyses, lung intravital microscopy, and adoptive transfer of ILC9 cells revealed that high IL-9 expression distinguishes a multicytokine-producing state-of-activated ILC2s with an increased capacity to initiate IL-5-dependent allergic airway inflammation. Similar to IL-33 and TSLP, TL1A is expressed in airway basal cells in healthy and asthmatic human lungs. Together, these results indicate that TL1A is an epithelium-derived cytokine and an important cofactor of IL-33 in the airways. |
