{"id":23220,"date":"2026-07-09T15:03:11","date_gmt":"2026-07-09T15:03:11","guid":{"rendered":"https:\/\/www.drfz.de\/?p=23220"},"modified":"2026-07-09T15:06:24","modified_gmt":"2026-07-09T15:06:24","slug":"cytokine-signaling-as-a-driver-of-kidney-damage-in-lupus-nephritis","status":"publish","type":"post","link":"https:\/\/www.drfz.de\/en\/neuigkeiten\/cytokine-signaling-as-a-driver-of-kidney-damage-in-lupus-nephritis\/","title":{"rendered":"Cytokine Signaling as a Driver of Kidney Damage in Lupus Nephritis"},"content":{"rendered":"\n<h2 class=\"wp-block-heading alignwide toc-item\" id=\"rethinking-t-cells-in-lupus-nephritis\"><strong>Rethinking T Cells in Lupus Nephritis<\/strong><\/h2>\n\n\n\n<p class=\"alignwide wp-block-paragraph\">New insights into lupus nephritis suggest that kidney damage may be driven less by autoantigen-specific T cells than by cytokine-mediated inflammatory activation. Using urine-derived kidney T cells from patients, Christopher Skopnik and colleagues from DRFZ and Charit\u00e9-University Medicine Berlin found little evidence for an antigen-driven mechanism but identified type I interferons and IL-15 as key triggers of pathogenic T-cell responses. Their findings highlight local T-cell activation and recruitment as promising therapeutic targets in lupus nephritis. These findings are published in Science Translational Medicine.<\/p>\n\n\n\n<p class=\"alignwide wp-block-paragraph\">Lupus nephritis (LN) is a severe autoimmune disease in which inflammation causes kidney damage. If left untreated, LN can lead to kidney failure, loss of organ function, and ultimately the need for dialysis or kidney transplantation. Although T cells are known to contribute to kidney injury in LN, their precise role has remained controversial. A clearer understanding of the underlying mechanisms could reveal new therapeutic targets and improve patient care.<\/p>\n\n\n\n<p class=\"alignwide wp-block-paragraph\">Two principal mechanisms by which kidney-infiltrating T cells may contribute to tissue damage have been proposed: (i) direct cytotoxicity through recognition of kidney-specific autoantigens, or (ii) antigen-independent activation that indirectly amplifies local inflammation.<\/p>\n\n\n\n<p class=\"alignwide wp-block-paragraph\">Skopnik and colleagues from DRFZ and the Department of Nephrology and Medical Intensive Care Charit\u00e9-University Medicine Berlin applied an innovative approach and isolated kidney tissue derived T cells from urine of patients. Using single-cell sequencing and in vitro experiments, they found little evidence supporting an (auto) antigen-driven mechanism. In contrast, they identified systemic and local cytokine stimulation, particularly by type I interferons (IFN-I) and interleukin-15 (IL-15), as a driver of pathogenic T cell activity in LN. Normally, IFN-I and IL-15 coordinate the immune responses against pathogens like viruses. In LN, however, these cytokines appear to aberrantly activate T cells, promoting the release of pro-inflammatory mediators including interferon gamma (IFN-\u03b3), tumor necrosis factor (TNF), and the cytotoxic molecules granzyme B and granzyme K. Together, these factors may induce collateral damage to kidney tissue and sustain chronic inflammation. <br>Moreover, Skopnik et al. observed that several kidney-infiltrating T cells expressed receptors specific for Epstein\u2013Barr virus (EBV) or Cytomegalovirus (CMV), despite the absence of detectable viral infection within the kidney tissue itself.<\/p>\n\n\n\n<p class=\"alignwide wp-block-paragraph\">Their findings support therapeutic strategies targeting T-cell recruitment into the kidney or their local cytokine-mediated activation as promising approaches for the treatment of LN.<\/p>\n\n\n\n  <section id=\"originalpublikation\" class=\"section links-list  alignwide  toc-item\">\n    <div class=\"container container--center\">\n                        <h2 class=\"section__heading launimation slideBottom\">Original publication<\/h2>\n        \n              \n      <div class=\"links-list__items-wrap\">\n        \n<div class=\"links-list__items links-list__items--row \">\n      <div class=\"links-list__item  launimation slideBottom\">\n      \n      <a href=\"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adz2015\" target=\"_self\" class=\"h6 links-list__item-title\">Skopnik CM, Klocke J, Freund P, Metzke D, Ostendorf L, Bunse M, Prskalo L, Kotzbauer J, Hinze C, Grothgar E, Goerlich N, Wagner L, Daniel C, Hartmann A, Schneider U, Biesen R, Alexander T, Hauser AE, Radbruch A, Eckardt KU, Hiepe F, Kruglov A, Mashreghi MF, Enghard P. Cytokine-mediated activation of kidney-infiltrating CD8+ T cells enables their contribution to inflammation in human lupus nephritis. Sci Transl Med. 2026 Jul 8;18(857):eadz2015. doi: 10.1126\/scitranslmed.adz2015. Epub 2026 Jul 8. PMID: 42418559.<\/a>\n\n      \n      <a href=\"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adz2015\" target=\"_self\" class=\"links-list__item-link\">\n        <span class=\"button button--arrow button--arrow-nw button--arrow-link\" ><\/span>\n      <\/a>\n    <\/div>\n  <\/div>\n      <\/div>\n    <\/div>\n  <\/section>\n\n","protected":false},"excerpt":{"rendered":"<p>Rethinking T Cells in Lupus Nephritis New insights into lupus nephritis suggest that kidney damage may be driven less by autoantigen-specific T cells than by\u2026<\/p>\n","protected":false},"author":4,"featured_media":23221,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[288,291],"tags":[497],"programme-area-tax":[182],"working-group-tax":[],"class_list":["post-23220","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-for-patients","category-publications","tag-program-area-4","programme-area-tax-programme-area-4"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.0 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Cytokine Signaling as a Driver of Kidney Damage in Lupus Nephritis - DRFZ<\/title>\n<meta name=\"description\" content=\"Christopher Skopnik of DRFZ and Charit\u00e9 demonstrates that cytokine signals drive kidney damage in lupus nephritis.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, 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