Sensory neurons promote immune homeostasis in the lung

Masato Tamari; Kate L. Del Bel; Aaron M. Ver Heul; Lydia Zamidar; Keisuke Orimo; Masato Hoshi; Anna M. Trier; Hiroshi Yano; Ting Lin Yang; Catherine M. Biggs; Kenichiro Motomura; Rintaro Shibuya; Chuyue D. Yu; Zili Xie; Hisato Iriki; Zhen Wang; Kelsey Auyeung; Gargi Damle; Deniz Demircioglu; Jill K. Gregory; Dan Hasson; Jinye Dai; Rui B. Chang; Hideaki Morita; Kenji Matsumoto; Sanjay Jain; Steven Van Dyken; Joshua D. Milner; Dusan Bogunovic; Hongzhen Hu; David Artis; Stuart E. Turvey; Brian S. Kim

doi:10.1016/j.cell.2023.11.027

Sensory neurons promote immune homeostasis in the lung

Masato Tamari, Kate L. Del Bel, Aaron M. Ver Heul, Lydia Zamidar, Keisuke Orimo, Masato Hoshi, Anna M. Trier, Hiroshi Yano, Ting Lin Yang, Catherine M. Biggs, Kenichiro Motomura, Rintaro Shibuya, Chuyue D. Yu, Zili Xie, Hisato Iriki, Zhen Wang, Kelsey Auyeung, Gargi Damle, Deniz Demircioglu, Jill K. GregoryDan Hasson, Jinye Dai, Rui B. Chang, Hideaki Morita, Kenji Matsumoto, Sanjay Jain, Steven Van Dyken, Joshua D. Milner, Dusan Bogunovic, Hongzhen Hu, David Artis, Stuart E. Turvey, Brian S. Kim

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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 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.

Original language	English
Pages (from-to)	44-61.e17
Journal	Cell
Volume	187
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2023.11.027
State	Published - Jan 4 2024

Keywords

AAV
CGRP
ILC2
JAK1
afferent nerves
allergic lung inflammation
atopic disorders
neuropeptide
sensory neurons
vagus nerve

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10.1016/j.cell.2023.11.027

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Tamari, M., Del Bel, K. L., Ver Heul, A. M., Zamidar, L., Orimo, K., Hoshi, M., Trier, A. M., Yano, H., Yang, T. L., Biggs, C. M., Motomura, K., Shibuya, R., Yu, C. D., Xie, Z., Iriki, H., Wang, Z., Auyeung, K., Damle, G., Demircioglu, D., ... Kim, B. S. (2024). Sensory neurons promote immune homeostasis in the lung. Cell, 187(1), 44-61.e17. https://doi.org/10.1016/j.cell.2023.11.027

@article{d0f2d895c571480b8997cb5497f2ee44,

title = "Sensory neurons promote immune homeostasis in the lung",

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 (JAK1GoF) 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.",

keywords = "AAV, CGRP, ILC2, JAK1, afferent nerves, allergic lung inflammation, atopic disorders, neuropeptide, sensory neurons, vagus nerve",

author = "Masato Tamari and {Del Bel}, {Kate L.} and {Ver Heul}, {Aaron M.} and Lydia Zamidar and Keisuke Orimo and Masato Hoshi and Trier, {Anna M.} and Hiroshi Yano and Yang, {Ting Lin} and Biggs, {Catherine M.} and Kenichiro Motomura and Rintaro Shibuya and Yu, {Chuyue D.} and Zili Xie and Hisato Iriki and Zhen Wang and Kelsey Auyeung and Gargi Damle and Deniz Demircioglu and Gregory, {Jill K.} and Dan Hasson and Jinye Dai and Chang, {Rui B.} and Hideaki Morita and Kenji Matsumoto and Sanjay Jain and {Van Dyken}, Steven and Milner, {Joshua D.} and Dusan Bogunovic and Hongzhen Hu and David Artis and Turvey, {Stuart E.} and Kim, {Brian S.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2024",

month = jan,

day = "4",

doi = "10.1016/j.cell.2023.11.027",

language = "English",

volume = "187",

pages = "44--61.e17",

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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 & Kim, BS 2024, 'Sensory neurons promote immune homeostasis in the lung', Cell, vol. 187, no. 1, pp. 44-61.e17. https://doi.org/10.1016/j.cell.2023.11.027

TY - JOUR

T1 - Sensory neurons promote immune homeostasis in the lung

AU - Tamari, Masato

AU - Del Bel, Kate L.

AU - Ver Heul, Aaron M.

AU - Zamidar, Lydia

AU - Orimo, Keisuke

AU - Hoshi, Masato

AU - Trier, Anna M.

AU - Yano, Hiroshi

AU - Yang, Ting Lin

AU - Biggs, Catherine M.

AU - Motomura, Kenichiro

AU - Shibuya, Rintaro

AU - Yu, Chuyue D.

AU - Xie, Zili

AU - Iriki, Hisato

AU - Wang, Zhen

AU - Auyeung, Kelsey

AU - Damle, Gargi

AU - Demircioglu, Deniz

AU - Gregory, Jill K.

AU - Hasson, Dan

AU - Dai, Jinye

AU - Chang, Rui B.

AU - Morita, Hideaki

AU - Matsumoto, Kenji

AU - Jain, Sanjay

AU - Van Dyken, Steven

AU - Milner, Joshua D.

AU - Bogunovic, Dusan

AU - Hu, Hongzhen

AU - Artis, David

AU - Turvey, Stuart E.

AU - Kim, Brian S.

PY - 2024/1/4

Y1 - 2024/1/4

N2 - 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 (JAK1GoF) 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.

AB - 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 (JAK1GoF) 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.

KW - AAV

KW - CGRP

KW - ILC2

KW - JAK1

KW - afferent nerves

KW - allergic lung inflammation

KW - atopic disorders

KW - neuropeptide

KW - sensory neurons

KW - vagus nerve

UR - http://www.scopus.com/inward/record.url?scp=85181134398&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2023.11.027

DO - 10.1016/j.cell.2023.11.027

M3 - Article

C2 - 38134932

AN - SCOPUS:85181134398

SN - 0092-8674

VL - 187

SP - 44-61.e17

JO - Cell

JF - Cell

IS - 1

ER -

Sensory neurons promote immune homeostasis in the lung

Abstract

Keywords

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