{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:14:11Z","timestamp":1791850451706,"version":"4.3.4"},"reference-count":90,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6721","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:p>The innate immune system shapes brain development and is implicated in neurodevelopmental diseases. It is critical to define the relevant immune cells and signals and their impact on brain circuits. In this work, we found that group 2 innate lymphoid cells (ILC2s) and their cytokine interleukin-13 (IL-13) signaled directly to inhibitory interneurons to increase inhibitory synapse density in the developing mouse brain. ILC2s expanded and produced IL-13 in the developing brain meninges. Loss of ILC2s or IL-13 signaling to interneurons decreased inhibitory, but not excitatory, cortical synapses. Conversely, ILC2s and IL-13 were sufficient to increase inhibitory synapses. Loss of this signaling pathway led to selective impairments in social interaction. These data define a type 2 neuroimmune circuit in early life that shapes inhibitory synapse development and behavior.<\/jats:p>","DOI":"10.1126\/science.adi1025","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T13:59:00Z","timestamp":1730383140000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":61,"title":["Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior"],"prefix":"10.1126","volume":"386","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8983-3126","authenticated-orcid":true,"given":"Jerika J.","family":"Barron","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences\u2013Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4781-8518","authenticated-orcid":true,"given":"Nicholas M.","family":"Mroz","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7210-8614","authenticated-orcid":true,"given":"Sunrae E.","family":"Taloma","sequence":"additional","affiliation":[{"name":"Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"Kavli Institute for Fundamental Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8640-0157","authenticated-orcid":true,"given":"Madelene W.","family":"Dahlgren","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"Lung Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7727-9674","authenticated-orcid":true,"given":"Jorge F.","family":"Ortiz-Carpena","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2477-2975","authenticated-orcid":true,"given":"Matthew G.","family":"Keefe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences\u2013Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline C.","family":"Escoubas","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences\u2013Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5511-887X","authenticated-orcid":true,"given":"Leah C.","family":"Dorman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences\u2013Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"Chan-Zuckerberg Biohub, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3190-8524","authenticated-orcid":true,"given":"Ilia D.","family":"Vainchtein","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences\u2013Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8753-1469","authenticated-orcid":true,"given":"Pailin","family":"Chiaranunt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences\u2013Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8102-6346","authenticated-orcid":true,"given":"Maya E.","family":"Kotas","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2345-4964","authenticated-orcid":true,"given":"Tomasz J.","family":"Nowakowski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences\u2013Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7084-1532","authenticated-orcid":true,"given":"Kevin J.","family":"Bender","sequence":"additional","affiliation":[{"name":"Kavli Institute for Fundamental Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0764-3175","authenticated-orcid":true,"given":"Ari B.","family":"Molofsky","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4709-2411","authenticated-orcid":true,"given":"Anna V.","family":"Molofsky","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences\u2013Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"Kavli Institute for Fundamental Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13334"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.187"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.02.011"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109249"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1843-6"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0426-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00967-6"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-070918-050421"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0539-5"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2016.12.002"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac9593"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.06.002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091419"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18626"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aag2638"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601546"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aay5199"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0776-4"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.10.022"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.04.019"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.03.014"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.031"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.01.071"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161982"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal3589"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.050"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20220605"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.12.001"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2018.04.003"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-102319-103410"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.86130"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.348190.120"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00716-4"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.01.011"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0393-4"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","unstructured":"R. T. Han I. D. Vainchtein J. C. M. Schlachetzki F. S. Cho L. C. Dorman T. Johung E. Ahn J. T. Barron H. Nakao-Inoue A. Joshi Ari. B. Molofsky C. K. Glass J. T. Paz A. V. Molofsky Interleukin-33 coordinates a microglial phagocytic response and limits corticothalamic excitability and seizure susceptibility. bioRxiv 2021.08.05.455250 [Preprint] (2021); https:\/\/doi.org\/10.1101\/2021.08.05.455250.10.1101\/2021.08.05.455250","DOI":"10.1101\/2021.08.05.455250"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0201-4"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.014"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3582"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121964"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12526"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.10.009"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0139-6"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.02.002"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.12.014"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.06.033"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095906"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.021"},{"key":"e_1_3_2_50_2","unstructured":"L. C. Dorman P. T. Nguyen C. C. Escoubas I. D. Vainchtein Y. Xiao P. V. Lidsky H. Nakajo N. J. Silva C. Lagares-Linares E. Y. Wang S. E. Taloma B. Cuevas H. Nakao-Inoue B. M. Rivera B. Schwer C. Condello R. Andino T. J. Nowakowski A. V. Molofsky A type I interferon response defines a conserved microglial state required for effective neuronal phagocytosis. bioRxiv 2021.04.29.441889 [Preprint] (2022); https:\/\/doi.org\/10.1101\/2021.04.29.441889.10.1101\/2021.04.29.441889"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00107-4"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.05.018"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04915-7"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00508-z"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.04.011"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3155"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0314"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aao2304"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20211887"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.12.003"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35806-8"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2453-z"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01029-1"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06993-7"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-9-366"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-022-07784-7"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05418-8"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4407"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.3791\/1938"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24638"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.08.039"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2004.00071.x"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2851"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10339-011-0430-z"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159832"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6786-5_23"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2467"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05746"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2182"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1715"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003988107"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02236"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.12.7302"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.862101"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.05.028"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.12.001"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9781107415324.004"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.adi1025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T13:59:28Z","timestamp":1730383168000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.adi1025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":90,"journal-issue":{"issue":"6721","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1126\/science.adi1025"],"URL":"https:\/\/doi.org\/10.1126\/science.adi1025","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.03.16.532850","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2023-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-22","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadi1025"}}