Cited by 1,251Multiple Sclerosis Research StudiesT-cell and B-cell ImmunologyGut microbiota and health

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Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination

Berer, Kerstin, Mues, Marsilius, Koutrolos, Michail, Rasbi, Zakeya Al, Boziki, Marina, Johner, Caroline, Wekerle, Hartmut, Krishnamoorthy, Gurumoorthy·2011·Nature

DOI 10.1038/nature10554

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Abstract

Active multiple sclerosis lesions show inflammatory changes suggestive of a combined attack by autoreactive T and B lymphocytes against brain white matter. These pathogenic immune cells derive from progenitors that are normal, innocuous components of the healthy immune repertoire but become autoaggressive upon pathological activation. The stimuli triggering this autoimmune conversion have been commonly attributed to environmental factors, in particular microbial infection. However, using the relapsing-remitting mouse model of spontaneously developing experimental autoimmune encephalomyelitis, here we show that the commensal gut flora-in the absence of pathogenic agents-is essential in triggering immune processes, leading to a relapsing-remitting autoimmune disease driven by myelin-specific CD4(+) T cells. We show further that recruitment and activation of autoantibody-producing B cells from the endogenous immune repertoire depends on availability of the target autoantigen, myelin oligodendrocyte glycoprotein (MOG), and commensal microbiota. Our observations identify a sequence of events triggering organ-specific autoimmune disease and these processes may offer novel therapeutic targets.

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Authors: Berer, K., Mues, M., Koutrolos, M., Rasbi, Z. A., Boziki, M., Johner, C., Wekerle, H., & Krishnamoorthy, G.
Affiliations: Max Planck Institute of Neurobiology (DE)
Max Planck Society (DE)
Corresponding author: Wekerle, Hartmut
Krishnamoorthy, Gurumoorthy
ORCID: Rasbi, Zakeya Al
Boziki, Marina
Wekerle, Hartmut
Krishnamoorthy, Gurumoorthy
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2011-10-26
Volume: 479
Issue: 7374
Pages: 538-541
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature10554
OpenAlex: W2037907937
Cited by: 1,251
References: 29
Citations by year: 2026: 34 · 2025: 45 · 2024: 74 · 2023: 78 · 2022: 107 · 2021: 101 · 2020: 100 · 2019: 93 · 2018: 110 · 2017: 105 · 2016: 113 · 2015: 87 · 2014: 74 · 2013: 72 · 2012: 47
FWCI: 44.88
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Max Planck Digital Library (submittedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
Funders: Division of Materials Research
Topics: Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords: commensal gut microbiota, myelin autoantigens, myelin oligodendrocyte glycoprotein, multiple sclerosis, experimental autoimmune encephalomyelitis, autoimmune demyelination, autoantibody-producing B cells, CD4+ T cells, diet and microbiome, relapsing-remitting multiple sclerosis
MeSH terms: Animals, Autoantigens, B-Lymphocytes, Brain, Cell Movement, Diet, Encephalomyelitis, Autoimmune, Experimental, Germ-Free Life, Lymph Nodes, Lymphocyte Activation, Myelin Proteins, Myelin Sheath, Stomach, T-Lymphocytes, Autoimmunity, Cytokines, Germinal Center, Adoptive Transfer, Multiple Sclerosis, Relapsing-Remitting, Mice, Metagenome, Myelin-Oligodendrocyte Glycoprotein

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Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination

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