{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:03:43Z","timestamp":1792047823566,"version":"4.4.0"},"reference-count":30,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6504","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK115217"],"award-info":[{"award-number":["1R01DK115217"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2020,8,7]]},"abstract":"Interferons interfere with lung repair<\/jats:title>\n \n Interferons (IFNs) are central to antiviral immunity. Viral recognition elicits IFN production, which in turn triggers the transcription of IFN-stimulated genes (ISGs), which engage in various antiviral functions. Type I IFNs (IFN-\u03b1 and IFN-\u03b2) are widely expressed and can result in immunopathology during viral infections. By contrast, type III IFN (IFN-\u03bb) responses are primarily restricted to mucosal surfaces and are thought to confer antiviral protection without driving damaging proinflammatory responses. Accordingly, IFN-\u03bb has been proposed as a therapeutic in coronavirus disease 2019 (COVID-19) and other such viral respiratory diseases (see the Perspective by Grajales-Reyes and Colonna). Broggi\n et al.<\/jats:italic>\n report that COVID-19 patient morbidity correlates with the high expression of type I and III IFNs in the lung. Furthermore, IFN-\u03bb secreted by dendritic cells in the lungs of mice exposed to synthetic viral RNA causes damage to the lung epithelium, which increases susceptibility to lethal bacterial superinfections. Similarly, using a mouse model of influenza infection, Major\n et al.<\/jats:italic>\n found that IFN signaling (especially IFN-\u03bb) hampers lung repair by inducing p53 and inhibiting epithelial proliferation and differentiation. Complicating this picture, Hadjadj\n et al.<\/jats:italic>\n observed that peripheral blood immune cells from severe and critical COVID-19 patients have diminished type I IFN and enhanced proinflammatory interleukin-6\u2013 and tumor necrosis factor-\u03b1\u2013fueled responses. This suggests that in contrast to local production, systemic production of IFNs may be beneficial. The results of this trio of studies suggest that the location, timing, and duration of IFN exposure are critical parameters underlying the success or failure of therapeutics for viral respiratory infections.\n <\/jats:p>\n \n Science<\/jats:italic>\n , this issue p.\n 706<\/jats:related-article>\n , p.\n 712<\/jats:related-article>\n , p.\n 718<\/jats:related-article>\n ; see also p.\n 626<\/jats:related-article>\n <\/jats:p>","DOI":"10.1126\/science.abc3545","type":"journal-article","created":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T19:05:27Z","timestamp":1591902327000},"page":"706-712","source":"Crossref","is-referenced-by-count":403,"title":["Type III interferons disrupt the lung epithelial barrier upon viral recognition"],"prefix":"10.1126","volume":"369","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-2401","authenticated-orcid":true,"given":"Achille","family":"Broggi","sequence":"first","affiliation":[{"name":"Harvard Medical School, Boston Children\u2019s Hospital, Division of Immunology, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2956-4830","authenticated-orcid":true,"given":"Sreya","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston Children\u2019s Hospital, Division of Immunology, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-187X","authenticated-orcid":true,"given":"Benedetta","family":"Sposito","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston Children\u2019s Hospital, Division of Immunology, Boston, MA, USA."},{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Spreafico","sequence":"additional","affiliation":[{"name":"Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-9472","authenticated-orcid":true,"given":"Fabio","family":"Balzarini","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston Children\u2019s Hospital, Division of Immunology, Boston, MA, USA."},{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5888-3668","authenticated-orcid":true,"given":"Antonino","family":"Lo Cascio","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston Children\u2019s Hospital, Division of Immunology, Boston, MA, USA."},{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-9861","authenticated-orcid":true,"given":"Nicola","family":"Clementi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Microbiology and Virology, Vita-Salute San Raffaele University, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3196-1336","authenticated-orcid":true,"given":"Maria","family":"De Santis","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center - IRCCS, Rozzano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0637-0910","authenticated-orcid":true,"given":"Nicasio","family":"Mancini","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Microbiology and Virology, Vita-Salute San Raffaele University, Milan, Italy."},{"name":"IRCCS San Raffaele Hospital, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7046-4914","authenticated-orcid":true,"given":"Francesca","family":"Granucci","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy."},{"name":"National Institute of Molecular Genetics (INGM) \u201cRomeo ed Enrica Invernizzi,\u201d Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3423-7474","authenticated-orcid":true,"given":"Ivan","family":"Zanoni","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston Children\u2019s Hospital, Division of Immunology, Boston, MA, USA."},{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy."},{"name":"Harvard Medical School, Boston Children\u2019s Hospital, Division of Gastroenterology, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190295"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3821"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.04.025"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140995"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0331-4"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200653"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00114-19"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01939-15"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3231"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2020.104364"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126363"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000849"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc2061"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.026"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.04.017"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3665"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04734"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233632"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.164"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214935"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13412-5"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)33221-0"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2196-x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1702.100282"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03326"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0182-z"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700250"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa4304"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00819-17"},{"key":"e_1_3_2_31_2","unstructured":"K. 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