1. Sensory neurons promote immune homeostasis in the lung.
- Author
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Tamari M, Del Bel KL, Ver Heul AM, Zamidar L, Orimo K, Hoshi M, Trier AM, Yano H, Yang TL, Biggs CM, Motomura K, Shibuya R, Yu CD, Xie Z, Iriki H, Wang Z, Auyeung K, Damle G, Demircioglu D, Gregory JK, Hasson D, Dai J, Chang RB, Morita H, Matsumoto K, Jain S, Van Dyken S, Milner JD, Bogunovic D, Hu H, Artis D, Turvey SE, and Kim BS
- Subjects
- Animals, Humans, Mice, Cytokines, Inflammation, Lymphocytes, Dermatitis, Atopic immunology, Immunity, Innate, Lung immunology, Sensory Receptor Cells enzymology
- Abstract
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 JAK1GoF 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., Competing Interests: Declaration of interests B.S.K. is founder of KliRNA Biotech; he has served as a consultant for 23andMe, ABRAX Japan, AbbVie, Almirall, Amgen, Arcutis Biotherapeutics, Arena Pharmaceuticals, argenx, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Clexio Biosciences, Eli Lilly and Company, Escient Pharmaceuticals, Evommune, Galderma, Genentech, GlaxoSmithKline, Granular Therapeutics, Incyte Corporation, Innovaderm Research, Janssen, Kiniksa, LEO Pharma, Maruho, Novartis, Pfizer, Recens Medical, Regeneron Pharmaceuticals, Sanofi, Septerna, Triveni Bio, Vial, and WebMD; he has stock in ABRAX Japan, KliRNA Biotech, Locus Biosciences, and Recens Medical; he holds a patent for the use of JAK1 inhibitors for chronic pruritus; and he has a patent pending for the use of JAK inhibitors for interstitial cystitis. D.A. has contributed to scientific advisory boards at Pfizer, Takeda, FARE, and the KRF. D.B. is the founder of Lab11 Therapeutics.., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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