{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:43:30Z","timestamp":1791398610316,"version":"4.3.3"},"reference-count":74,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"100","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2024,10,18]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1126\/sciimmunol.adl2986","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T13:58:16Z","timestamp":1729259896000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":16,"title":["An ILC2-chitinase circuit restores lung homeostasis after epithelial injury"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2209-8638","authenticated-orcid":true,"given":"Haerin","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0160-3092","authenticated-orcid":true,"given":"Do-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-9919","authenticated-orcid":true,"given":"Roberto Efra\u00edn","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Michael","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology, Washington University Gnotobiotic Core Facility, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Summer","family":"Rucknagel","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology, Washington University Gnotobiotic Core Facility, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauryn","family":"Mosby","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8261-7439","authenticated-orcid":true,"given":"Yilin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjana","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8510-1385","authenticated-orcid":true,"given":"Emma S.","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, MO, USA."},{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed O.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9344-9004","authenticated-orcid":true,"given":"Baoling","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8791-3165","authenticated-orcid":true,"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, MO, USA."},{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA."},{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA."},{"name":"Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA."},{"name":"Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-6867","authenticated-orcid":true,"given":"Richard M.","family":"Locksley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA."},{"name":"Department of Medicine, University of California, San Francisco, San Francisco, CA, USA."},{"name":"Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5080-2859","authenticated-orcid":true,"given":"James S.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9787-0883","authenticated-orcid":true,"given":"Steven J.","family":"Van Dyken","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1702747"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30505-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201709-1883OC"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.03.009"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2020.109941"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.119410"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100972"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.12.1071"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.03.044"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201042109"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.02.003"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.59"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.add5649"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2588-y"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01689-12"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30183-5"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05746"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13173"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.08.014"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.001"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc3172"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.14.4.8600933"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57673"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25786"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17358-3"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-0542-8"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.06.020"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03570-8"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03569-1"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abo5070"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-031621-024344"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5387"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abo7728"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300014"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004053"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2131"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.41"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3582"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.011"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200810-1615OC"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202004-1274OC"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200689"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1509070112"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.18.1.2740"},{"key":"e_1_3_2_46_2","first-page":"L728","article-title":"Transforming growth factor-alpha enhances alveolar epithelial cell repair in a new in vitro model","volume":"267","author":"Kheradmand F.","year":"1994","unstructured":"F. Kheradmand, H. G. Folkesson, L. Shum, R. Derynk, R. Pytela, M. A. Matthay, Transforming growth factor-alpha enhances alveolar epithelial cell repair in a new in vitro model. Am. J. Physiol. 267, L728\u2013L738 (1994).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-019-0477-8"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05297-6"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.08.001"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0417OC"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02073-x"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0602-4"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0449-8"},{"key":"e_1_3_2_54_2","doi-asserted-by":"crossref","unstructured":"R. R. Ricardo-Gonzalez M. E. Kotas I. Tenvooren D. M. Marquez M. S. Fassett J. Lee S. G. Daniel K. Bittinger R. E. D\u00edaz J. S. Fraser K. Mark Ansel M. H. Spitzer H.-E. Liang R. M. Locksley Type 2 innate immunity regulates hair follicle homeostasis to control Demodex pathosymbionts. bioRxiv 437438 [Preprint] (2021); https:\/\/doi.org\/10.1101\/2021.03.29.437438.","DOI":"10.1101\/2021.03.29.437438"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.012443"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msw198"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2011.02.017"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.05.097"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3822"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2182"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00107-4"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110799"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.89918.3"},{"key":"e_1_3_2_64_2","unstructured":"Qupath software; https:\/\/qupath.github.io\/."},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv412"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-161"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/986048"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0201-4"},{"key":"e_1_3_2_72_2","unstructured":"mm10 transcriptome_1; ftp:\/\/ftp.ensembl.org\/pub\/release-84\/fasta\/mus_musculus\/dna\/Mus_musculus.GRCm38.dna.primary_assembly.fa.gz."},{"key":"e_1_3_2_73_2","unstructured":"mm10 transcriptome_2; ftp:\/\/ftp.ensembl.org\/pub\/release-84\/gtf\/mus_musculus\/Mus_musculus.GRCm38.84.gtf.gz."},{"key":"e_1_3_2_74_2","unstructured":"LungMAP Consortium; www.lungmap.net."},{"key":"e_1_3_2_75_2","unstructured":"H. Jung S. Van Dyken Lung distal epithelium_ChiaRed and WT epithelial cells (Dryad 2024)."}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.adl2986","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T13:58:23Z","timestamp":1729259903000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.adl2986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,18]]},"references-count":74,"journal-issue":{"issue":"100","published-print":{"date-parts":[[2024,10,18]]}},"alternative-id":["10.1126\/sciimmunol.adl2986"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.adl2986","relation":{},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,18]]},"assertion":[{"value":"2023-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-15","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadl2986"}}