{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:14:51Z","timestamp":1789906491092,"version":"4.0.1"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Peritoneal dialysis (PD) employs hypertonic glucose to remove excess water and uremic waste. Peritoneal membrane failure limits its long\u2010term use. T\u2010cell cytokines promote this decline. T\u2010cell differentiation is critically determined by the microenvironment. We here study how PD\u2010range hypertonic glucose regulates T\u2010cell polarization and IL\u201017 production.<\/jats:p>\n                  <jats:p>\n                    In the human peritoneal cavity, CD3\n                    <jats:sup>+<\/jats:sup>\n                    cell numbers increased in PD. Single cell RNA sequencing detected expression of T helper (Th) 17 signature genes\n                    <jats:italic>RORC<\/jats:italic>\n                    and\n                    <jats:italic>IL23R<\/jats:italic>\n                    . In vitro, PD\u2010range glucose stimulated spontaneous and amplified cytokine\u2010induced Th17 polarization. Osmotic controls\n                    <jats:sc>l<\/jats:sc>\n                    \u2010glucose and\n                    <jats:sc>d<\/jats:sc>\n                    \u2010mannose demonstrate that induction of IL\u201017A is a substance\u2010independent, tonicity dose\u2010dependent process. PD\u2010range glucose upregulated glycolysis and increased the proportion of dysfunctional mitochondria. Blockade of reactive\u2010oxygen species (ROS) prevented IL\u201017A induction in response to PD\u2010range glucose. Peritoneal mesothelium cultured with IL\u201017A or IL17F produced pro\u2010inflammatory cytokines IL\u20106, CCL2, and CX3CL1. In PD patients, peritoneal IL\u201017A positively correlated with CX3CL1 concentrations. PD\u2010range glucose\u2010stimulated, but neither identically treated\n                    <jats:italic>\n                      Il17a\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      Il17f\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    nor T\u00a0cells cultured with the ROS scavenger N\u2010acetylcysteine enhanced mesothelial CX3CL1 expression.\n                  <\/jats:p>\n                  <jats:p>Our data delineate PD\u2010range hypertonic glucose as a novel inducer of Th17 polarization in a mitochondrial\u2010ROS\u2010dependent manner. Modulation of tonicity\u2010mediated effects of PD solutions may improve membrane survival.<\/jats:p>","DOI":"10.1002\/eji.202048733","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T12:25:46Z","timestamp":1601036746000},"page":"354-367","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Peritoneal dialysate\u2010range hypertonic glucose promotes T\u2010cell IL\u201017 production that induces mesothelial inflammation"],"prefix":"10.1002","volume":"51","author":[{"given":"Alexandra","family":"Helmke","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"H\u00fcsing","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Gaedcke","sequence":"additional","affiliation":[{"name":"German Center for Lung Research, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Brauns","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Balzer","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Reinhardt","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Hiss","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelli","family":"Shushakova","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"de Luca","sequence":"additional","affiliation":[{"name":"German Center for Lung Research, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8789-9578","authenticated-orcid":false,"given":"Immo","family":"Prinz","sequence":"additional","affiliation":[{"name":"Hannover Medical School Institute for Immunology  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Haller","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3217-5433","authenticated-orcid":false,"given":"Sibylle","family":"von Vietinghoff","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01694"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00738"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40200-017-0297-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.03.040"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01853"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.021"},{"key":"e_1_2_8_8_1","first-page":"217","article-title":"Interleukin\u201017 cytokines: effectors and targets in psoriasis\u2014a breakthrough in understanding and treatment","author":"Prinz I.","year":"2020","journal-title":"J. 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