{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:36:22Z","timestamp":1784950582620,"version":"3.55.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["668036"],"award-info":[{"award-number":["668036"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health and Medical Research Council of Australia","award":["1115805"],"award-info":[{"award-number":["1115805"]}]},{"name":"National Health and Medical Research Council of Australia","award":["2008921"],"award-info":[{"award-number":["2008921"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and hypothesis<\/jats:title>\n                  <jats:p>Increased T-cell interkeukin (IL)-7R\u03b1 signalling is associated with a poorer prognosis in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. These studies examined the functional role of IL-7R\u03b1 (CD127) in experimental glomerulonephritis mediated by anti-myeloperoxidase (MPO) T-cell autoimmunity. We hypothesized that T cells would express IL-7R\u03b1 in the kidney and that blocking the function of IL-7R\u03b1, without cellular depletion, would be protective.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Mice were immunized with mouse MPO, then low-dose sheep anti-mouse basement membrane globulin was administered to trigger glomerulonephritis. Flow cytometry and RNA-sequencing characterized intrarenal CD127+-expressing CD4+ and CD8+ T cells in mice with anti-MPO glomerulonephritis. To assess the functional role of IL-7R\u03b1, mice with established anti-MPO autoimmunity were treated with anti-IL-7R\u03b1 antibodies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Control ovalbumin-immunized mice given anti-basement membrane globulin developed minimal injury, while MPO-immunized mice given anti-basement membrane globulin developed albuminuria with glomerular and tubulointerstitial injury. Numbers of intrarenal IL-7R\u03b1+ (CD127+) CD4+ and CD8+ T cells were increased in mice with anti-MPO glomerulonephritis. There were 3738 and 2726 genes differentially expressed between intrarenal CD127\u2212PD-1+ and CD127+PD-1\u2212 CD8+ and CD4+ T cells, respectively, with substantially overlapping differentially expressed genes between CD8+ and CD4+ T cells. Both CD127\u2212PD-1+ CD8+ and CD4+ T cells were enriched for previously described T-cell exhaustion signatures associated with prognosis in autoimmune disease. As effector memory T cells drive inflammation, we blocked the IL-7R\u03b1 after inducing anti-MPO autoimmunity. Anti-IL-7R\u03b1 antibodies limited histological injury, and reduced albuminuria numbers of glomerular and interstitial leucocytes, with reduced intrarenal chemokine and pro-inflammatory cytokine expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Intrarenal effector memory and exhausted CD4+ and CD8+ T cells are present in experimental anti-MPO glomerulonephritis. Neutralizing effector T cells via the IL-7R\u03b1 after the induction of autoimmunity limits intrarenal inflammation and disease. IL-7R\u03b1 may be a therapeutic target in ANCA-associated vasculitis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfae276","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T01:48:08Z","timestamp":1732240088000},"page":"1350-1361","source":"Crossref","is-referenced-by-count":2,"title":["Neutralizing the IL-7R\u03b1 limits injury in experimental ANCA-associated glomerulonephritis"],"prefix":"10.1093","volume":"40","author":[{"given":"Maliha A","family":"Alikhan","sequence":"first","affiliation":[{"name":"Monash University Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, , Clayton, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Kishimoto","sequence":"additional","affiliation":[{"name":"Monash University Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, , Clayton, 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