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000309833 1001_ $$00009-0005-7492-4307$$aRaschdorf, Annika$$b0
000309833 245__ $$aColonic spatial single-cell proteomics and murine models link mitochondrial dysfunction to dimeric IgA-secreting plasma cell deficiency in Crohn's disease.
000309833 260__ $$a[London]$$bSpringer Nature$$c2026
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000309833 520__ $$aSecretory 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.
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000309833 650_7 $$2NLM Chemicals$$aImmunoglobulin A, Secretory
000309833 650_2 $$2MeSH$$aAnimals
000309833 650_2 $$2MeSH$$aCrohn Disease: immunology
000309833 650_2 $$2MeSH$$aCrohn Disease: metabolism
000309833 650_2 $$2MeSH$$aCrohn Disease: pathology
000309833 650_2 $$2MeSH$$aPlasma Cells: metabolism
000309833 650_2 $$2MeSH$$aPlasma Cells: immunology
000309833 650_2 $$2MeSH$$aPlasma Cells: pathology
000309833 650_2 $$2MeSH$$aColon: immunology
000309833 650_2 $$2MeSH$$aColon: pathology
000309833 650_2 $$2MeSH$$aColon: metabolism
000309833 650_2 $$2MeSH$$aMice
000309833 650_2 $$2MeSH$$aMitochondria: metabolism
000309833 650_2 $$2MeSH$$aMitochondria: pathology
000309833 650_2 $$2MeSH$$aDisease Models, Animal
000309833 650_2 $$2MeSH$$aHumans
000309833 650_2 $$2MeSH$$aProteomics: methods
000309833 650_2 $$2MeSH$$aSingle-Cell Analysis
000309833 650_2 $$2MeSH$$aImmunoglobulin A, Secretory: metabolism
000309833 650_2 $$2MeSH$$aImmunoglobulin A, Secretory: immunology
000309833 650_2 $$2MeSH$$aMale
000309833 650_2 $$2MeSH$$aFemale
000309833 650_2 $$2MeSH$$aIntestinal Mucosa: immunology
000309833 650_2 $$2MeSH$$aIntestinal Mucosa: metabolism
000309833 650_2 $$2MeSH$$aIntestinal Mucosa: pathology
000309833 650_2 $$2MeSH$$aMice, Inbred C57BL
000309833 650_2 $$2MeSH$$aCell Differentiation
000309833 650_2 $$2MeSH$$aB-Lymphocytes: immunology
000309833 650_2 $$2MeSH$$aB-Lymphocytes: metabolism
000309833 650_2 $$2MeSH$$aOxidative Phosphorylation
000309833 7001_ $$00000-0003-2974-433X$$ade Almeida, Larissa Nogueira$$b1
000309833 7001_ $$aSolbach, Philipp$$b2
000309833 7001_ $$aKirstein, Martha M$$b3
000309833 7001_ $$00000-0002-8314-2682$$aMarquardt, Jens U$$b4
000309833 7001_ $$aSchmelter, Franziska$$b5
000309833 7001_ $$00000-0001-8464-3756$$aGünther, Ulrich L$$b6
000309833 7001_ $$aSchlichting, Heidi$$b7
000309833 7001_ $$aHicken, Maren$$b8
000309833 7001_ $$00009-0001-0595-1425$$aChristiansen, Lea$$b9
000309833 7001_ $$aWiestler, Miriam$$b10
000309833 7001_ $$aTews, Hauke C$$b11
000309833 7001_ $$aBettenworth, Dominik$$b12
000309833 7001_ $$aconsortium, OUTLIVE-CRC$$b13$$eCollaboration Author
000309833 7001_ $$0P:(DE-He78)7483734fd8ab316391aa604c95f0e98a$$aSültmann, Holger$$b14$$udkfz
000309833 7001_ $$aPeipp, Matthias$$b15
000309833 7001_ $$00000-0001-9181-8067$$aValerius, Thomas$$b16
000309833 7001_ $$00009-0009-7537-1651$$aRagab, Mohab$$b17
000309833 7001_ $$aSauer, Thorben$$b18
000309833 7001_ $$aGemoll, Timo$$b19
000309833 7001_ $$00000-0002-5383-8603$$aEhlers, Marc$$b20
000309833 7001_ $$00000-0002-9692-8828$$aRosenstiel, Philip$$b21
000309833 7001_ $$00000-0003-1263-7693$$aManz, Rudolf A$$b22
000309833 7001_ $$00000-0003-0692-2105$$aKünstner, Axel$$b23
000309833 7001_ $$aBusch, Hauke$$b24
000309833 7001_ $$aSina, Christian$$b25
000309833 7001_ $$00000-0002-6142-5577$$aDerer, Stefanie$$b26
000309833 7001_ $$aKatalinic, Alexander$$b27$$eContributor
000309833 7001_ $$aOberländer, Martina$$b28$$eContributor
000309833 7001_ $$aDeck, Ruth$$b29$$eContributor
000309833 7001_ $$0P:(DE-He78)7483734fd8ab316391aa604c95f0e98a$$aSültmann, Holger$$b30$$eContributor
000309833 7001_ $$avon Bubnoff, Nikolas$$b31$$eContributor
000309833 7001_ $$aHutzenlaub, Tobias$$b32$$eContributor
000309833 7001_ $$aJülg, Peter$$b33$$eContributor
000309833 7001_ $$aBurziwoda, Dominik$$b34$$eContributor
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