Sensory neurons promote immune homeostasis in the lung

作者：Masato Tamari, Kate L. Del Bel, Aaron Ver Heul, Lydia Zamidar, Keisuke Orimo, Masato Hoshi, Anna M. Trier, Hiroshi Yano, Ting-Lin Yang, Catherine M. Biggs, Kenichiro Motomura, Rintaro Shibuya, Chuyue Yu, Zili Xie, Hisato Iriki, Zhen Wang, Kelsey Auyeung, Gargi Damle, Deniz Demircioğlu, Jill Gregory, Dan Hasson, Jinye Dai, Rui B. Chang, Hideaki Morita, Kenji Matsumoto, Sanjay Jain, Steven J. Van Dyken, Joshua D. Milner, Dusan Bogunovic, Hongzhen Hu, David Artis, Stuart E. Turvey, Brian Kim · 发表于：Cell · 年份：2023 · DOI：10.1016/j.cell.2023.11.027 · 被引用次数：122 · 研究领域：Asthma and respiratory diseases、Stress Responses and Cortisol、IL-33, ST2, and ILC Pathways

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 /CGRPβ was dependent on JAK1 in the vagus nerve, and CGRPβ 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.