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Although macrophages play a pivotal role in UC pathogenesis, how KARAP regulates macrophage immune responses remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, KARAP expression was assessed in peripheral blood mononuclear cells (PBMCs) and colonic tissues from patients with UC using quantitative real-time PCR and immunofluorescence. Dextran sulfate sodium (DSS)-induced colitis was established in KARAP knockout (KARAP\u207b\/\u207b) and wild-type (WT) mice. In addition, macrophages isolated from KARAP\u207b\/\u207b and WT mice were cocultured with intestinal epithelial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>KARAP expression was increased in PBMCs from patients with UC and was particularly high in macrophages. In the DSS-induced colitis model, KARAP deficiency improved intestinal barrier integrity by preserving macrophage mitochondrial homeostasis. KARAP blockade also increased interleukin (IL)-10 expression, thereby further preserving intestinal mucosal barrier integrity. Mechanistically, increased IL-10 expression depended on enhanced mechanistic target of rapamycin (mTOR)\/mitophagy-mediated mitochondrial homeostasis in KARAP\u207b\/\u207b macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings indicate that KARAP contributes to the regulation of intestinal mucosal barrier integrity by modulating macrophage mitochondrial homeostasis and IL-10 expression. Overall, these results offer new insight into the potential of KARAP as a new target for UC treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/pcmedi\/pbag027","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:24:50Z","timestamp":1790335490000},"source":"Crossref","is-referenced-by-count":0,"title":["KARAP deficiency alleviates intestinal mucosal barrier dysfunction by regulating mitochondrial homeostasis in macrophages"],"prefix":"10.1093","volume":"9","author":[{"given":"Guiyuan","family":"Jin","sequence":"first","affiliation":[{"name":"Affiliated Hospital of Jining Medical University Department of Gastroenterology, , Jining 272029 ,","place":["China"]},{"name":"Jining Key Laboratory of Digestive Immunology, Affiliated Hospital of Jining Medical University , Jining 272029 ,","place":["China"]},{"name":"Medical Research Center, Affiliated Hospital of Jining Medical University , Jining 272029 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Yang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Jining Medical University Department of Gastroenterology, , Jining 272029 ,","place":["China"]},{"name":"Jining Key Laboratory of Digestive Immunology, Affiliated Hospital of Jining Medical University , Jining 272029 ,","place":["China"]},{"name":"Medical Research Center, Affiliated Hospital of Jining Medical University , Jining 272029 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengqin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Jining Medical University Department of Gastroenterology, , Jining 272029 ,","place":["China"]},{"name":"Jining Key Laboratory of Digestive Immunology, Affiliated Hospital of Jining Medical University , Jining 272029 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Jining Medical University Department of Gastroenterology, , Jining 272029 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Jining Medical University Department of Gastroenterology, , Jining 272029 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanjun","family":"Dong","sequence":"additional","affiliation":[{"name":"Jining Key Laboratory of Basic and Clinical Transformation of Autoimmune Diseases, Jining Medical University , Jining 272067 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Research Center, Affiliated Hospital of Jining Medical University , Jining 272029 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7803-605X","authenticated-orcid":false,"given":"Guangxi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Jining Medical University Department of Gastroenterology, , Jining 272029 ,","place":["China"]},{"name":"Jining Key Laboratory of Digestive Immunology, Affiliated Hospital of Jining Medical University , Jining 272029 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"2026102111495181200_bib1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3390\/nu14020269","article-title":"Vitamin D in inflammatory bowel diseases. 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