{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:16:07Z","timestamp":1788419767613,"version":"build-2803163510"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Immunoglobulin A nephropathy (IgAN) is a chronic glomerular disease characterized by mesangial IgA deposition, which can progress to end-stage renal failure. Tonsillectomy is used as a therapeutic intervention to slow disease progression and provide early clinical benefit. However, the immune mechanisms within the palatine tonsils that contribute to IgAN pathogenesis remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To define the tonsillar immune environment that regulates pathological antibody production, we analyzed T and B lymphocyte subsets in relation to renal function. We also conducted functional studies to evaluate the production of galactose-deficient IgA (Gd-IgA) and anti-Tn (GalNAc-Ser\/Thr) antibodies, both of which are implicated in the formation of pathogenic immune complexes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Interfollicular T follicular helper (IF-Tfh) cells (CD3\n                      <jats:sup>+<\/jats:sup>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>-<\/jats:sup>\n                      PD-1\n                      <jats:sup>lo<\/jats:sup>\n                      CXCR5\n                      <jats:sup>lo<\/jats:sup>\n                      ) were significantly expanded in IgAN tonsils compared with disease controls and strongly correlated with clinical markers of renal abnormalities. Transcriptomic analysis of IF-Tfh cells from IgAN tonsils revealed a distinct gene expression profile enriched for effector memory T cell\u2013like features associated with kidney impairment. Functional studies demonstrated that IF-Tfh cells potently promoted class-switched memory B cells to produce Gd-IgA1 and anti-Tn (GalNAc-Ser\/Thr) antibodies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that an IF-Tfh cell\u2013dominant immune environment drives IgAN pathogenesis and may represent a target for noninvasive therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1848238","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:43:17Z","timestamp":1788417797000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tonsillar Tfh cells contribute to the pathogenesis of IgA nephropathy in collaboration with memory B 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