TY - JOUR
T1 - An ILC2-chitinase circuit restores lung homeostasis after epithelial injury
AU - Jung, Haerin
AU - Kim, Do Hyun
AU - Díaz, Roberto Efraín
AU - White, J. Michael
AU - Rucknagel, Summer
AU - Mosby, Lauryn
AU - Wang, Yilin
AU - Reddy, Sanjana
AU - Winkler, Emma S.
AU - Hassan, Ahmed O.
AU - Ying, Baoling
AU - Diamond, Michael S.
AU - Locksley, Richard M.
AU - Fraser, James S.
AU - Van Dyken, Steven J.
N1 - Publisher Copyright:
Copyright © 2024 the authors.
PY - 2024/10
Y1 - 2024/10
N2 - Environmental exposures increase the risk for severe lung disease, but specific drivers of persistent epithelial injury and immune dysfunction remain unclear. Here, we identify a feedback circuit triggered by chitin, a common component of airborne particles, that affects lung health after epithelial injury. In mice, epithelial damage disrupts lung chitinase activity, leading to environmental chitin accumulation, impaired epithelial renewal, and group 2 innate lymphoid cell (ILC2) activation. ILC2s, in turn, restore homeostasis by inducing acidic mammalian chitinase (AMCase) in regenerating epithelial cells and promoting chitin degradation, epithelial differentiation, and inflammatory resolution. Mice lacking AMCase or ILC2s fail to clear chitin and exhibit increased mortality and impaired epithelial regeneration after injury. These effects are ameliorated by chitinase replacement therapy, demonstrating that chitin degradation is crucial for recovery after various forms of lung perturbation. Thus, the ILC2-chitinase response circuit may serve as a target for alleviating persistent postinjury lung epithelial and immune dysfunction.
AB - Environmental exposures increase the risk for severe lung disease, but specific drivers of persistent epithelial injury and immune dysfunction remain unclear. Here, we identify a feedback circuit triggered by chitin, a common component of airborne particles, that affects lung health after epithelial injury. In mice, epithelial damage disrupts lung chitinase activity, leading to environmental chitin accumulation, impaired epithelial renewal, and group 2 innate lymphoid cell (ILC2) activation. ILC2s, in turn, restore homeostasis by inducing acidic mammalian chitinase (AMCase) in regenerating epithelial cells and promoting chitin degradation, epithelial differentiation, and inflammatory resolution. Mice lacking AMCase or ILC2s fail to clear chitin and exhibit increased mortality and impaired epithelial regeneration after injury. These effects are ameliorated by chitinase replacement therapy, demonstrating that chitin degradation is crucial for recovery after various forms of lung perturbation. Thus, the ILC2-chitinase response circuit may serve as a target for alleviating persistent postinjury lung epithelial and immune dysfunction.
UR - http://www.scopus.com/inward/record.url?scp=85206801752&partnerID=8YFLogxK
U2 - 10.1126/sciimmunol.adl2986
DO - 10.1126/sciimmunol.adl2986
M3 - Article
C2 - 39423283
AN - SCOPUS:85206801752
SN - 2470-9468
VL - 9
JO - Science immunology
JF - Science immunology
IS - 100
M1 - eadl2986
ER -