PXD069842-1

PXD069842 is an original dataset announced via ProteomeXchange.

Title	Colonic spatial single-cell proteomics and murine models link mitochondrial dysfunction to dimeric IgA-secreting plasma cell deficiency in Crohn's disease
Description	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.
HostingRepository	PRIDE
AnnounceDate	2026-01-13
AnnouncementXML	Submission_2026-01-13_07:18:34.702.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thorben Sauer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-23 13:44:51	ID requested
⏵ 1	2026-01-13 07:18:35	announced

Dataset with its publication pending

submitter keyword: None

Prof. Dr.
contact affiliation	University Hospital Schleswig-Holstein, Campus Lübeck, Department of Surgery
contact email	timo.gemoll@uni-luebeck.de
lab head
Thorben Sauer
contact affiliation	Department of Surgery, Laboratory for Surgical Research, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck Germany
contact email	thorben.sauer@student.uni-luebeck.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069842
     1. Label: PRIDE project
     2. Name: Colonic spatial single-cell proteomics and murine models link mitochondrial dysfunction to dimeric IgA-secreting plasma cell deficiency in Crohn's disease