{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:23:07Z","timestamp":1768508587847,"version":"3.49.0"},"posted":{"date-parts":[[2023,11,21]]},"group-title":"Immunology","reference-count":83,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Allergic asthma is a chronic respiratory disease that initiates in early life, but causal mechanisms are poorly understood. Here we examined how prenatal inflammation shapes allergic asthma susceptibility by reprogramming lung immunity from early development. Induction of Type I interferon-mediated inflammation during development provoked expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produced increased IL-5 and IL-13, and were associated with acute Th2 bias, eosinophilia, and decreased Tregs in the lung. The hyperactive ILC2 phenotype was recapitulated by adoptive transfer of a fetal liver precursor following exposure to prenatal inflammation, indicative of developmental programming. Programming of ILC2 function and subsequent lung immune remodeling by prenatal inflammation led to airway dysfunction at baseline and in response to papain, indicating increased asthma susceptibility. Our data provide a link by which developmental programming of progenitors by early-life inflammation drives lung immune remodeling and asthma susceptibility through hyperactivation of lung-resident ILC2s.<\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Prenatal inflammation programs asthma susceptibility by inducing the production of hyperactivated ILC2s in the developing lung.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.11.20.567899","type":"posted-content","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T17:05:43Z","timestamp":1700586343000},"source":"Crossref","is-referenced-by-count":0,"title":["Prenatal inflammation reprograms hyperactive ILC2s that promote allergic lung inflammation and airway dysfunction"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3989-3785","authenticated-orcid":false,"given":"Diego A.","family":"L\u00f3pez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleah","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena Moreno","family":"Aguilar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra-Deering","family":"Rice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth J.","family":"Myers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristi J.","family":"Warren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2498-9469","authenticated-orcid":false,"given":"Robert","family":"Welner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8580-8660","authenticated-orcid":false,"given":"Anna E.","family":"Beaudin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023112312150408000_2023.11.20.567899v1.1","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1111\/j.1651-2227.2003.tb00840.x","article-title":"Infection-induced wheezing during the first year of life does not mean asthma: a 50-year-old observation","volume":"92","year":"2003","journal-title":"Acta Paediatr"},{"key":"2023112312150408000_2023.11.20.567899v1.2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200406-730OC"},{"key":"2023112312150408000_2023.11.20.567899v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)10321-5"},{"key":"2023112312150408000_2023.11.20.567899v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2768"},{"key":"2023112312150408000_2023.11.20.567899v1.5","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200804-579OC"},{"key":"2023112312150408000_2023.11.20.567899v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20273"},{"key":"2023112312150408000_2023.11.20.567899v1.7","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201104-0660OC"},{"key":"2023112312150408000_2023.11.20.567899v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.06.006"},{"key":"2023112312150408000_2023.11.20.567899v1.9","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1093\/clinchem\/hvaa089","article-title":"Type I Interferon in Children with Viral or Bacterial Infections","volume":"66","year":"2020","journal-title":"Clin Chem"},{"key":"2023112312150408000_2023.11.20.567899v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394299-9.00003-5"},{"key":"2023112312150408000_2023.11.20.567899v1.11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00123"},{"key":"2023112312150408000_2023.11.20.567899v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/nri3786"},{"key":"2023112312150408000_2023.11.20.567899v1.13","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2014.942288"},{"key":"2023112312150408000_2023.11.20.567899v1.14","doi-asserted-by":"crossref","unstructured":"G. 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