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Gut-microbiota specific IgA B cells traffic to the CNS in multiple sclerosis

ABSTRACT: Gut-microbiota specific IgA B cells traffic to the CNS in multiple sclerosis

PROVIDER: PRJEB32763 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	ERR4682180_1.fastq.gz	Fastqsanger.gz
	ERR4682180_2.fastq.gz	Fastqsanger.gz
	ERR4682190_1.fastq.gz	Fastqsanger.gz
	ERR4682190_2.fastq.gz	Fastqsanger.gz

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Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis

Project description:Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis

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Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis.

Project description:Changes in gut microbiota composition and a diverse role of B cells have recently been implicated in multiple sclerosis (MS), a central nervous system (CNS) autoimmune disease. Immunoglobulin A (IgA) is a key regulator at the mucosal interface. However, whether gut microbiota shape IgA responses and what role IgA+ cells have in neuroinflammation are unknown. Here, we identify IgA-bound taxa in MS and show that IgA-producing cells specific for MS-associated taxa traffic to the inflamed CNS, resulting in a strong, compartmentalized IgA enrichment in active MS and other neuroinflammatory diseases. Unlike previously characterized polyreactive anti-commensal IgA responses, CNS IgA cross-reacts with surface structures on specific bacterial strains but not with brain tissue. These findings establish gut microbiota-specific IgA+ cells as a systemic mediator in MS and suggest a critical role of mucosal B cells during active neuroinflammation with broad implications for IgA as an informative biomarker and IgA-producing cells as an immune subset to harness for therapeutic interventions.

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Microbiota, IgA and Multiple Sclerosis.

Project description:Multiple sclerosis (MS) is a neuroinflammatory disease characterized by immune cell infiltration in the central nervous system and destruction of myelin sheaths. Alterations of gut bacteria abundances are present in MS patients. In mouse models of neuroinflammation, depletion of microbiota results in amelioration of symptoms, and gavage with MS patient microbiota exacerbates the disease and inflammation via Th17 cells. On the other hand, depletion of B cells using anti-CD20 is an efficient therapy in MS, and growing evidence shows an important deleterious role of B cells in MS pathology. However, the failure of TACI-Ig treatment in MS highlighted the potential regulatory role of plasma cells. The mechanism was recently demonstrated involving IgA+ plasma cells, specific for gut microbiota and producing IL-10. IgA-coated bacteria in MS patient gut exhibit also modifications. We will focus our review on IgA interactions with gut microbiota and IgA+ B cells in MS. These recent data emphasize new pathways of neuroinflammation regulation in MS.

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Bioinformatics Analyses Determined the Distinct CNS and Peripheral Surrogate Biomarker Candidates between Two Mouse Models for Progressive Multiple Sclerosis

Project description:Previously, we have established two distinct progressive multiple sclerosis (MS) models by induction of experimental autoimmune encephalomyelitis (EAE) with myelin oligodendrocyte glycoprotein (MOG) in two mouse strains. A.SW mice develop ataxia with antibody deposition, but no T cell infiltration, in the central nervous system (CNS), while SJL/J mice develop paralysis with CNS T cell infiltration. In this study, we determined biomarkers contributing to the heterogeneities of the two models. Using the CNS and spleen microarray transcriptome and cytokine data, we conducted computational supervised analyses (volcano plot, heat map, and pathway analysis) and unsupervised principal component analysis (PCA) with pattern matching analysis (PMA).

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Project description:Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis

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Proteomic analysis in multiple sclerosis

Project description:To address the differential response of the CNS, proteomics was applied in experimental autoimmune encephalomyelitis (EAE) mice and cuprizone (CPZ) mice in two different CNS regions

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Human brain tissues from healthy controls and multiple sclerosis patients

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2019-04-29 | GSE123496 | GEO

Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism [2]

Project description:IgA+ Plasma Cells were sort-purified from the small intestinal lamina prorpia of C57BL/6 mice at four Zeitgeber time points (ZT0, 6, 12 and 18). RNA extracted from these samples was subjected to bulk RNA seq to identify time of day differences in IgA+ PC gene expression.

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