| First Author | Tamari M | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 1 | Pages | 44-61.e17 |
| PubMed ID | 38134932 | Mgi Jnum | J:352422 |
| Mgi Id | MGI:7574004 | Doi | 10.1016/j.cell.2023.11.027 |
| Citation | Tamari M, et al. (2024) Sensory neurons promote immune homeostasis in the lung. Cell 187(1):44-61.e17 |
| abstractText | Cytokines employ downstream Janus kinases (JAKs) to promote chronic inflammatory diseases. JAK1-dependent type 2 cytokines drive allergic inflammation, and patients with JAK1 gain-of-function (GoF) variants develop atopic dermatitis (AD) and asthma. To explore tissue-specific functions, we inserted a human JAK1 GoF variant (JAK1(GoF)) into mice and observed the development of spontaneous AD-like skin disease but unexpected resistance to lung inflammation when JAK1(GoF) expression was restricted to the stroma. We identified a previously unrecognized role for JAK1 in vagal sensory neurons in suppressing airway inflammation. Additionally, expression of Calcb/CGRPbeta was dependent on JAK1 in the vagus nerve, and CGRPbeta suppressed group 2 innate lymphoid cell function and allergic airway inflammation. Our findings reveal evolutionarily conserved but distinct functions of JAK1 in sensory neurons across tissues. This biology raises the possibility that therapeutic JAK inhibitors may be further optimized for tissue-specific efficacy to enhance precision medicine in the future. |
