{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:54:20Z","timestamp":1791557660088,"version":"4.3.4"},"reference-count":52,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6731","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2025,1,17]]},"abstract":"<jats:p>The immune system shapes body metabolism, while interactions between peripheral neurons and immune cells control tissue homeostasis and immunity. However, whether peripheral neuroimmune interactions orchestrate endocrine system functions remains unexplored. After fasting, mice lacking type 2 innate lymphoid cells (ILC2s) displayed disrupted glucose homeostasis, impaired pancreatic glucagon secretion, and inefficient hepatic gluconeogenesis. Additionally, intestinal ILC2s were found in the pancreas, which was dependent on their expression of the adrenergic beta 2 receptor. Targeted activation of catecholaminergic intestinal neurons promoted the accumulation of ILC2s in the pancreas. Our work provides evidence that immune cells can be regulated by neuronal signals in response to fasting, activating an inter-organ communication route that promotes pancreatic endocrine function and regulation of blood glucose levels.<\/jats:p>","DOI":"10.1126\/science.adi3624","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T18:58:52Z","timestamp":1737053932000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":45,"title":["Neuronal-ILC2 interactions regulate pancreatic glucagon and glucose homeostasis"],"prefix":"10.1126","volume":"387","author":[{"given":"Marko","family":"\u0160estan","sequence":"first","affiliation":[{"name":"Champalimaud Foundation. Champalimaud Centre for the Unknown. Champalimaud Research. Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Raposo","sequence":"additional","affiliation":[{"name":"Champalimaud Foundation. Champalimaud Centre for the Unknown. Champalimaud Research. Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Rendas","sequence":"additional","affiliation":[{"name":"Champalimaud Foundation. Champalimaud Centre for the Unknown. Champalimaud Research. Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brea","sequence":"additional","affiliation":[{"name":"Champalimaud Foundation. Champalimaud Centre for the Unknown. Champalimaud Research. Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roksana","family":"Pirzgalska","sequence":"additional","affiliation":[{"name":"Champalimaud Foundation. Champalimaud Centre for the Unknown. Champalimaud Research. Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Rasteiro","sequence":"additional","affiliation":[{"name":"Champalimaud Foundation. Champalimaud Centre for the Unknown. Champalimaud Research. Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Aliseychik","sequence":"additional","affiliation":[{"name":"Champalimaud Foundation. Champalimaud Centre for the Unknown. Champalimaud Research. Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas","family":"Godinho","sequence":"additional","affiliation":[{"name":"Champalimaud Foundation. Champalimaud Centre for the Unknown. Champalimaud Research. Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9lder","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Champalimaud Foundation. Champalimaud Centre for the Unknown. Champalimaud Research. Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Champalimaud Foundation. Champalimaud Centre for the Unknown. Champalimaud Research. Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Wueest","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetology, University Children\u2019s Hospital, University of Zurich, Zurich, Switzerland."},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital, University of Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Konrad","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetology, University Children\u2019s Hospital, University of Zurich, Zurich, Switzerland."},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital, University of Zurich, Zurich, Switzerland."},{"name":"Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique","family":"Veiga-Fernandes","sequence":"additional","affiliation":[{"name":"Champalimaud Foundation. Champalimaud Centre for the Unknown. Champalimaud Research. Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00063.2017"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2074-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2016.6"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2016.3"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI88876"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2015.93"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00443-x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0849-9"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba8310"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.10.015"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33171-6"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2018.05.001"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042718-041812"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0247-z"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aap9598"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.02.017"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048812"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-018-0063-y"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03830-7"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13440"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-620"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.00192.x"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3078"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam5809"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1579-3"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23469"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18644"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1210\/js.2016-1104"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21420"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4829"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.03.016"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2021.691777"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00413"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01456.x"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90030-G"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90029-C"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90047-0"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-9-49"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.03.005"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12526"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.90721"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0760-05.2005"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05395-5"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05297-6"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth762"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200809113"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80439-2"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1039\/c2ib00125j"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-117-3-806"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4612"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29588-8"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.08.018"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.adi3624","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T18:59:12Z","timestamp":1737053952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.adi3624"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,17]]},"references-count":52,"journal-issue":{"issue":"6731","published-print":{"date-parts":[[2025,1,17]]}},"alternative-id":["10.1126\/science.adi3624"],"URL":"https:\/\/doi.org\/10.1126\/science.adi3624","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,17]]},"assertion":[{"value":"2023-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-02","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadi3624"}}