Dataset Information

Colonic spatial single-cell proteomics and murine models link mitochondrial dysfunction to dimeric IgA-secreting plasma cell deficiency in Crohn's disease

ABSTRACT: Secretory IgA (SIgA) is critical for maintaining the intestinal barrier. A dysregulated B-cell compartment and altered Ig secretion have been well documented in Crohn’s disease (CD) patients, although their origin is unknown. To unravel the role of mucosal humoral immunity in CD pathogenesis, we in-depth phenotype colonic plasma cell (PC) differentiation in CD at the single-cell level, linked to ex vivo functional characterization and experimental mouse models with a congenital mitochondrial defect or under glucose-free high-protein dietary intervention. Here, we demonstrate that despite expanded colonic B cells, CD patients in remission present significantly diminished mucosal dimeric IgA and fecal SIgA. Colonic plasmablasts and immature CD19+CD45+ PCs are increased at the expense of the mature CD19-CD45- phenotype. Accordingly, CD-derived ex vivo differentiated PCs display impaired maturation into dimeric IgA-secreting PCs. In this study, patient-derived data from colonic RNA-seq, spatial single-cell proteomics, and plasma metabolomics are combined with data from both mouse models and highlight the crucial role of mitochondrial oxidative phosphorylation in colonic IgA+-PC differentiation, suggesting promising directions for future therapeutic strategies.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Thorben Sauer

LAB HEAD: Prof. Dr.

PROVIDER: PXD069842 | Pride | 2026-01-13

REPOSITORIES: Pride

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Colonic spatial single-cell proteomics and murine models link mitochondrial dysfunction to dimeric IgA-secreting plasma cell deficiency in Crohn's disease.

Raschdorf Annika A de Almeida Larissa Nogueira LN Solbach Philipp P Kirstein Martha M MM Marquardt Jens U JU Schmelter Franziska F Günther Ulrich L UL Schlichting Heidi H Hicken Maren M Christiansen Lea L Wiestler Miriam M Tews Hauke C HC Bettenworth Dominik D Peipp Matthias M Valerius Thomas T Ragab Mohab M Sauer Thorben T Gemoll Timo T Ehlers Marc M Rosenstiel Philip P Manz Rudolf A RA Künstner Axel A Busch Hauke H Sina Christian C Derer Stefanie S

Nature communications 20260212 1

Secretory IgA (SIgA) is critical for maintaining the intestinal barrier. A dysregulated B-cell compartment and altered Ig secretion have been well documented in Crohn's disease (CD) patients, although their origin is unknown. To unravel the role of mucosal humoral immunity in CD pathogenesis, we in-depth phenotype colonic plasma cell (PC) differentiation in CD at the single-cell level, linked to ex vivo functional characterization and experimental mouse models with a congenital mitochondrial def ...[more]

PMID: 41680132

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