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However, the mechanisms underlying ILC2 adhesion and migration in the kidney remain poorly understood. Here, we revealed the critical role of integrin \u03b14\u03b27 in mediating renal ILC2 adhesion and function. We found that integrin \u03b14\u03b27 enables the retention of ILC2s in the kidney by binding to VCAM-1, E-cadherin, or fibronectin on structural cells. Moreover, integrin \u03b14\u03b27 knockdown reduced the production of the reparative cytokine amphiregulin (Areg) by ILC2s. In lupus nephritis, TLR7\/9 signaling within the kidney microenvironment downregulates integrin \u03b14\u03b27 expression, leading to decreased Areg production and promoting the egress of ILC2s. Notably, IL-33 treatment upregulated integrin \u03b14\u03b27 and Areg expression in ILC2s, thereby enhancing survival and reducing inflammation in lupus nephritis. Together, these findings highlight the potential of targeting ILC2 adhesion as a therapeutic strategy for autoimmune kidney diseases.<\/jats:p>","DOI":"10.1038\/s41423-024-01178-2","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T18:24:05Z","timestamp":1716920645000},"page":"723-737","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The protective roles of integrin \u03b14\u03b27 and Amphiregulin-expressing innate lymphoid cells in lupus nephritis"],"prefix":"10.1038","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2638-5749","authenticated-orcid":false,"given":"Seungwon","family":"Ryu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Ah","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwoo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2233-9449","authenticated-orcid":false,"given":"Yong-Soo","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung Choul","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5978-512X","authenticated-orcid":false,"given":"Hye Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"1178_CR1","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/ni.3482","volume":"17","author":"H Spits","year":"2016","unstructured":"Spits H, Bernink JH, Lanier L. 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