{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:58:32Z","timestamp":1790636312697,"version":"4.1.0"},"reference-count":61,"publisher":"American Society for Clinical Investigation","issue":"10","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 0255A141,P01 AI123086"],"award-info":[{"award-number":["R01 0255A141,P01 AI123086"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,16]]},"abstract":"<jats:p>\n                    IL-17\u2013producing CD4\n                    <jats:sup>+<\/jats:sup>\n                    (Th17) cells are pathogenically linked to autoimmunity and, specifically, to autoimmune kidney disease. The newly recognized immunoregulatory functions of erythropoietin (EPO) and its predominant intrarenal source suggested that EPO physiologically regulates Th17 cell differentiation, thereby serving as a barrier to development of autoimmune kidney disease. Using in vitro studies of human and murine cells and in vivo models, we show that EPO ligation of its receptor (EPO-R) on CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells directly inhibits Th17 cell generation and promotes transdifferentiation of Th17 cells into IL-17\n                    <jats:sup>\u2013<\/jats:sup>\n                    FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Mechanistically, EPO\/EPO-R ligation abrogates upregulation of\n                    <jats:italic>SGK1<\/jats:italic>\n                    gene expression and blocks p38 activity to prevent SGK1 phosphorylation, thereby inhibiting RORC-mediated transcription of\n                    <jats:italic>IL17<\/jats:italic>\n                    and\n                    <jats:italic>IL23<\/jats:italic>\n                    receptor genes. In a murine model of Th17 cell\u2013dependent aristolochic acid\u2013induced interstitial kidney disease associated with reduced renal EPO production, we demonstrate that transgenic EPO overexpression or recombinant EPO (rEPO) administration limits Th17 cell formation and clinical\/histological disease expression. EPO\/EPO-R ligations on CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells abrogate, while absence of T cell\u2013expressed EPO-R augments, Th17 cell induction and clinical\/histological expression of pristane-induced glomerulonephritis (associated with decreased intrarenal EPO). rEPO prevents spontaneous glomerulonephritis and Th17 cell generation in MRL-\n                    <jats:italic>lpr<\/jats:italic>\n                    mice. Together, our findings indicate that EPO physiologically and therapeutically modulates Th17 cells to limit expression of Th17 cell\u2013associated autoimmune kidney disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.127428","type":"journal-article","created":{"date-parts":[[2019,4,23]],"date-time":"2019-04-23T12:01:26Z","timestamp":1556020886000},"source":"Crossref","is-referenced-by-count":33,"title":["Erythropoietin inhibits SGK1-dependent Th17 cell induction and Th17 cell\u2013dependent kidney disease"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4864-3809","authenticated-orcid":true,"given":"Chiara","family":"Donadei","sequence":"first","affiliation":[{"name":"Department of Medicine, Translational Transplant Research Center, Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Nephrology Dialysis and Renal Transplantation Unit, S. Orsola University Hospital, Bologna, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-5326","authenticated-orcid":true,"given":"Andrea","family":"Angeletti","sequence":"additional","affiliation":[{"name":"Department of Medicine, Translational Transplant Research Center, Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Nephrology Dialysis and Renal Transplantation Unit, S. Orsola University Hospital, Bologna, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Cantarelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Translational Transplant Research Center, Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Dipartimento di Medicina e Chirurgia (Universit\u00e0 di Parma), UO Nefrologia (Azienda Ospedaliera-Universitaria Parma), Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivette D.","family":"D\u2019Agati","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"La Manna","sequence":"additional","affiliation":[{"name":"Nephrology Dialysis and Renal Transplantation Unit, S. 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