{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:14:48Z","timestamp":1789906488716,"version":"4.0.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["NSFC 82370746"],"award-info":[{"award-number":["NSFC 82370746"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["NSFC 82170762"],"award-info":[{"award-number":["NSFC 82170762"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation of Guangdong Province, China","award":["2022A1515012637"],"award-info":[{"award-number":["2022A1515012637"]}]},{"name":"\u201cThree big\u201d Construction of Large Science Program of Sun Yat-sen University, China","award":["82000-18843406"],"award-info":[{"award-number":["82000-18843406"]}]},{"name":"China Chronic Kidney Disease Management Innovation Program","award":["202206080010"],"award-info":[{"award-number":["202206080010"]}]},{"name":"Guangdong Basic and Applied Basic Research Fund Enterprise Joint Fund","award":["2021B1515230005"],"award-info":[{"award-number":["2021B1515230005"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Peritoneal mucosal-associated invariant T (MAIT) cells were characterized by single-cell RNA sequencing, histological imaging, and flow cytometry.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Activation of MAIT cells modulated glucose metabolism in mesothelial cells by TCRV\n                            <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                            7.2-MHC class 1\u2013related protein 1 signaling and triggered peritoneal fibrogenesis.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pharmacological inhibition of MAIT cell function by acetyl-6-formylpterin mitigated peritoneal fibrosis.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis (PD) and abdominal surgeries, yet effective treatments remain elusive. Given the known roles of mucosal-associated invariant T (MAIT) cells in immune responses and fibrotic diseases, we investigated their involvement in PD-induced peritoneal fibrosis to identify potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used single-cell RNA sequencing and flow cytometry to characterize the activation and function of peritoneal MAIT cells in patients undergoing long-term PD. Our investigation focused on the molecular pathways activated by these cells, particularly the MHC class 1\u2013related protein 1 (MR1)-mediated interaction with mesothelial cells and subsequent activation of the mTOR complex 1 signaling pathway. We further assessed the effect of inhibiting MAIT cells on fibrogenesis using both\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      models and Mr1 knockout mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our study revealed that long-term PD significantly enhanced the activation of MAIT cells, particularly the proinflammatory MAIT17 subtype. These activated cells contributed to peritoneal fibrogenesis by binding to the MR1 receptor on mesothelial cells, which triggered hyperglycolysis through the mTOR complex 1 pathway, ultimately leading to fibrogenesis. Notably, we demonstrated that blocking the MR1\u2013MAIT interaction, either through genetic knockout or pharmacological inhibition with acetyl-6-formylpterin, effectively mitigated fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identified MAIT cells as crucial drivers of PD-induced peritoneal fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000000627","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T12:05:14Z","timestamp":1738065914000},"page":"1072-1087","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":10,"title":["Mucosal-Associated Invariant T (MAIT) Cell\u2013Mediated Immune Mechanisms of Peritoneal Dialysis\u2013Induced Peritoneal Fibrosis and Therapeutic Targeting"],"prefix":"10.1681","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0915-6557","authenticated-orcid":false,"given":"Yuxiang","family":"Sun","sequence":"first","affiliation":[{"name":"Nephrology Division, Department of Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"},{"name":"NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2052-1140","authenticated-orcid":false,"given":"Qiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"},{"name":"NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Sun","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6295-8212","authenticated-orcid":false,"given":"Hu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Guo","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Peng","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchun","family":"Lin","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4216-6004","authenticated-orcid":false,"given":"Canming","family":"Li","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Shang","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1371-2889","authenticated-orcid":false,"given":"Yanxu","family":"Chen","sequence":"additional","affiliation":[{"name":"Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 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