ArticleFrontiers in immunology2026
Spatially microdissected profiling of tonsillar germinal centers reveals a KLRG1-enriched immune signature in IgA nephropathy.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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-the central site for IgA class switching and mucosal B-cell activation-remain poorly characterized, particularly in relation to glomerular injury severity. Methods: In this exploratory case-control 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. Results: Laser microdissection revealed a GC-enriched immune signature in IgAN, characterized by upregulation of KLRG1 (fold change 3.2, p < 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-associated genes, consistent with a mucosal activation-associated pattern. Conclusion: 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.
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