{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:46:14Z","timestamp":1791222374590,"version":"4.1.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"50","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,12,16]]},"abstract":"<jats:p>\n                    Lupus nephritis (LN), which is characterized by the accumulation of DNA-containing immune complexes (ICs), is the leading cause of death in patients with systemic lupus erythematosus (SLE). While growing evidence highlights the central role of CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cells in shaping the immune landscape of regional tissues, mechanisms driving the cell differentiation in LN remain largely unexplored. In this study, we identified an increased frequency of CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cells within the kidneys of SLE patients. Importantly, glomerular endothelial cells (ECs) from human LN tissues were found to promote the differentiation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cells by upregulating B lymphocyte\u2013induced maturation protein 1 (Blimp-1). Genetic knockdown of Blimp-1 in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells resulted in a reduced frequency of renal CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cells and alleviated LN in humanized SLE chimeras. Mechanistically, LN-associated ECs, triggered by circulating DNA from SLE patients, exhibited elevated CD38 expression via the cGAS-STING signaling pathway. This facilitated the transfer of CD38 into CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells through an exosome-dependent mechanism, leading to the depletion of nicotinamide adenine dinucleotide (NAD\n                    <jats:sup>+<\/jats:sup>\n                    ) levels in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. The resulting NAD\n                    <jats:sup>+<\/jats:sup>\n                    depletion impaired the PARP1-mediated ADP-ribosylation of early growth response protein 1 (EGR1), which, in turn, enhanced Blimp-1 transcription and promoted CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation. Targeting the cGAS\/STING-CD38-EGR1 axis effectively reduced renal CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cell accumulation and inhibited LN progression in humanized SLE chimeras. Thus, ECs facilitate NAD\n                    <jats:sup>+<\/jats:sup>\n                    depletion to drive CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation, presenting a cellular mechanism underlying LN pathogenesis and a potential therapeutic target for the clinical management of human LN.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2507422122","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:37:41Z","timestamp":1765564661000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":6,"title":["Glomerular endothelial cells eliminate nicotinamide adenine dinucleotide to instruct CD103\n                    <sup>+<\/sup>\n                    T cells in human lupus nephritis"],"prefix":"10.1073","volume":"122","author":[{"given":"Li","family":"Jia","sequence":"first","affiliation":[{"name":"The Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University","place":["Suzhou, China"]},{"name":"Jiangsu Key Laboratory of Infection and Immunity, Minister of Education Key Laboratory of Geriatric Diseases and Immunology, Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Liu","sequence":"additional","affiliation":[{"name":"The Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University","place":["Suzhou, China"]},{"name":"Jiangsu Key Laboratory of Infection and Immunity, Minister of Education Key Laboratory of Geriatric Diseases and Immunology, Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyan","family":"Ji","sequence":"additional","affiliation":[{"name":"The Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University","place":["Suzhou, China"]},{"name":"Jiangsu Key Laboratory of Infection and Immunity, Minister of Education Key Laboratory of Geriatric Diseases and Immunology, Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Lei","sequence":"additional","affiliation":[{"name":"The Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University","place":["Suzhou, China"]},{"name":"Jiangsu Key Laboratory of Infection and Immunity, Minister of Education Key Laboratory of Geriatric Diseases and Immunology, Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danhua","family":"Su","sequence":"additional","affiliation":[{"name":"The Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University","place":["Suzhou, China"]},{"name":"Jiangsu Key Laboratory of Infection and Immunity, Minister of Education Key Laboratory of Geriatric Diseases and Immunology, Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyi","family":"Li","sequence":"additional","affiliation":[{"name":"The Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University","place":["Suzhou, China"]},{"name":"Jiangsu Key Laboratory of Infection and Immunity, Minister of Education Key Laboratory of Geriatric Diseases and Immunology, Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University, Wuxi People\u2019s Hospital, Wuxi Medical Center, Nanjing Medical University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University, Wuxi People\u2019s Hospital, Wuxi Medical Center, Nanjing Medical University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Zunyi Medical University","place":["Zunyi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Cao","sequence":"additional","affiliation":[{"name":"Renal Medicine, Faculty of Medicine and Health, Kolling Institute of Medical Research, Sydney Medical School, University of 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