| First Author | Hurrell BP | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 13 | Pages | 4509-4524.e5 |
| PubMed ID | 31875557 | Mgi Jnum | J:296927 |
| Mgi Id | MGI:6468841 | Doi | 10.1016/j.celrep.2019.11.102 |
| Citation | Hurrell BP, et al. (2019) TNFR2 Signaling Enhances ILC2 Survival, Function, and Induction of Airway Hyperreactivity. Cell Rep 29(13):4509-4524.e5 |
| abstractText | Group 2 innate lymphoid cells (ILC2s) can initiate pathologic inflammation in allergic asthma by secreting copious amounts of type 2 cytokines, promoting lung eosinophilia and airway hyperreactivity (AHR), a cardinal feature of asthma. We discovered that the TNF/TNFR2 axis is a central immune checkpoint in murine and human ILC2s. ILC2s selectively express TNFR2, and blocking the TNF/TNFR2 axis inhibits survival and cytokine production and reduces ILC2-dependent AHR. The mechanism of action of TNFR2 in ILC2s is through the non-canonical NF-kappaB pathway as an NF-kappaB-inducing kinase (NIK) inhibitor blocks the costimulatory effect of TNF-alpha. Similarly, human ILC2s selectively express TNFR2, and using hILC2s, we show that TNFR2 engagement promotes AHR through a NIK-dependent pathway in alymphoid murine recipients. These findings highlight the role of the TNF/TNFR2 axis in pulmonary ILC2s, suggesting that targeting TNFR2 or relevant signaling is a different strategy for treating patients with ILC2-dependent asthma. |
