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GI tumors from mice bearing heterozygous mutations in\n            <jats:italic>Stk11<\/jats:italic>\n            (which encodes LKB1) display signatures of pathogenic IL-17\u2013producing CD4\n            <jats:sup>+<\/jats:sup>\n            T helper 17 (T\n            <jats:sub>H<\/jats:sub>\n            17) cells. LKB1 constrains T cell inflammatory potential, as\n            <jats:italic>Stk11<\/jats:italic>\n            \/LKB1 haploinsufficiency promotes T cell differentiation toward pathogenic IL-17\u2013producing T cell lineages (CD4\n            <jats:sup>+<\/jats:sup>\n            T\n            <jats:sub>H<\/jats:sub>\n            17 and CD8\n            <jats:sup>+<\/jats:sup>\n            T\n            <jats:sub>c<\/jats:sub>\n            17) in vitro and following intestinal infection. Mechanistically, aberrant CREB-regulated transcription coactivator 2 (CRTC2)\u2013dependent signaling drives pathogenic T\n            <jats:sub>H<\/jats:sub>\n            17 cell programs downstream of LKB1 haploinsufficiency. Targeting this circuit via CRTC2 deletion or IL-17 blockade antagonizes GI polyp growth in mouse models of Peutz-Jeghers syndrome. These findings establish LKB1 as a gatekeeper of inflammatory type 3 (IL-17\u2013dependent) T cell responses and identify a CRTC2\u2013IL-17 signaling axis that can be targeted therapeutically to block the growth of LKB1 mutant GI tumors.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adt5933","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T13:58:33Z","timestamp":1750427913000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["IL-17 links the tumor suppressor LKB1 to gastrointestinal inflammation and polyposis"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-8032","authenticated-orcid":true,"given":"Shelby E.","family":"Compton","sequence":"first","affiliation":[{"name":"Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"DeCamp","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4147-2915","authenticated-orcid":true,"given":"Brandon M.","family":"Oswald","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-056X","authenticated-orcid":true,"given":"Susan M.","family":"Kitchen-Goosen","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7405-1551","authenticated-orcid":true,"given":"Kin H.","family":"Lau","sequence":"additional","affiliation":[{"name":"Bioinformatics and Biostatistics Core, Van Andel Institute, Grand Rapids, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Fillinger","sequence":"additional","affiliation":[{"name":"Bioinformatics and Biostatistics Core, Van Andel Institute, Grand Rapids, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2518-7129","authenticated-orcid":true,"given":"Michael S.","family":"Dahabieh","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1194-810X","authenticated-orcid":true,"given":"Alexandra Vander","family":"Ark","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-5986","authenticated-orcid":true,"given":"Connie M.","family":"Krawczyk","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA."},{"name":"Metabolism and Nutrition (MeNu) Program, Van Andel Institute, Grand Rapids, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2250-4675","authenticated-orcid":true,"given":"Russell G.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA."},{"name":"Metabolism and Nutrition (MeNu) Program, Van Andel Institute, Grand Rapids, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142702"},{"key":"e_1_3_2_3_2","first-page":"3659","article-title":"Inactivation of LKB1\/STK11 is a common event in adenocarcinomas of the lung","volume":"62","author":"Sanchez-Cespedes M.","year":"2002","unstructured":"M. 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