{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T11:04:24Z","timestamp":1772190264873,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1127514"],"award-info":[{"award-number":["1127514"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and hypothesis<\/jats:title>\n                    <jats:p>Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a major cause of glomerulonephritis (GN) and kidney failure and current therapies are often limited by significant toxicity and limitations. Regulatory T cells (Tregs) play a crucial role in maintaining immune tolerance, and their dysfunction has been implicated in AAV pathogenesis. Low dose interleukin-2 (IL-2) has emerged as a promising strategy to selectively expand Tregs and restore immune balance in several autoimmune diseases. However, low dose IL-2\u2019s therapeutic potential in AAV remains unclear, warranting further investigation into its immunoregulatory effects in experimental AAV models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We tested the therapeutic efficacy of low dose IL-2 therapy (25\u2009000 international units\/day) in an experimental murine model of AAV, specifically anti-myeloperoxidase (MPO) GN, using C57BL\/6J mice. Both passive and active models of anti-MPO GN were used to assess IL-2\u2019s effects across different disease settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In GN induced by passive transfer of anti-MPO antibodies, low dose IL-2 increased intrarenal Treg numbers, limited macrophage recruitment, and reduced macrophage pro-inflammatory phenotype in kidneys, demonstrating anti-inflammatory effects on innate immunity. However, these immunological changes did not translate into improvement in kidney injury. In T-cell mediated active anti-MPO GN induced by MPO immunization and triggered by anti-glomerular basement membrane globulin, preventative IL-2 therapy increased splenic Tregs, attenuated anti-MPO-specific Th1\/Th17 responses and limited structural and functional kidney injury. In established autoimmunity, mice treated with low dose IL-2 from 12 days after MPO immunization also expanded splenic Tregs. However, effector T-cell responses were also enhanced and glomerular injury was increased. To more specifically target Tregs and minimize low dose IL-2\u2019s potential to promote effector leukocytes, we administered IL-2 conjugated to an anti-IL-2 monoclonal antibody (IL-2\/anti-IL-2 immune complex). Although IL-2\/anti-IL-2 treatment increased Treg frequency in mice with established anti-MPO autoimmunity, it also paradoxically amplified anti-MPO T-cell effector responses and worsened glomerulonephritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In experimental anti-MPO GN, low dose IL-2 therapy has context specific effects on cellular and humoral immunity, and the potential for it to promote T effector responses in established autoimmunity may limit its utility in this condition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfaf178","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T11:47:05Z","timestamp":1756381625000},"page":"520-530","source":"Crossref","is-referenced-by-count":0,"title":["Low dose IL-2 administration prevents but fails to treat experimental autoimmune anti-myeloperoxidase 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