{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T07:05:04Z","timestamp":1779433504143,"version":"3.53.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"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>Background<\/jats:title>\n                    <jats:p>Geographic variability in the clinical efficacy of tonsillectomy for immunoglobulin A nephropathy (IgAN) suggests population-level differences in mucosal immune architecture. However, the molecular features of the tonsillar germinal center (GC) microenvironment\u2014the central site for IgA class switching and mucosal B-cell activation\u2014remain poorly characterized, particularly in relation to glomerular injury severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this exploratory case\u2013control study, we analyzed tonsils from biopsy-proven IgAN (n=5) and matched habitual tonsillitis controls (n=5). Laser microdissection was used to isolate GC plus mantle zone and non-GC regions, followed by immune transcriptomic profiling using the Nanostring Human Immunology V2 Panel. Differential expression was assessed with FDR correction. KLRG1 expression patterns were validated by immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Laser microdissection revealed a GC-enriched immune signature in IgAN, characterized by upregulation of KLRG1 (fold change 3.2, p &amp;lt; 0.001) and ZBTB16, alongside downregulation of CCL18, FADD, and TNFRSF17. Immunohistochemistry demonstrated GC-localized KLRG1 expression in IgAN, which appeared more evident in cases with crescentic glomerular lesions. Non-crescentic IgAN showed marginal GC localization, while controls exhibited predominantly extrafollicular KLRG1 expression. Whole-tissue analysis supported enrichment of innate-like lymphocyte\u2013associated genes, consistent with a mucosal activation\u2013associated pattern.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies a spatially defined, KLRG1-enriched GC signature in IgAN. These findings suggest a potential association between GC-localized KLRG1 expression and glomerular injury severity; however, given the exploratory nature and small sample size, they should be considered hypothesis-generating. Further studies are required to validate these observations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1750300","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T06:09:27Z","timestamp":1779430167000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatially microdissected profiling of tonsillar germinal centers reveals a KLRG1-enriched immune signature in IgA nephropathy"],"prefix":"10.3389","volume":"17","author":[{"given":"Mayuko","family":"Kawabe","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaro","family":"Ohki","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go","family":"Kanzaki","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine","place":["Tokyo, 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