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

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

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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Crossref · 10.1038/nature10554

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  • IL-17 pathway inhibitors (secukinumab and ixekizumab) are effective in treating psoriatic arthritis.

    “Similar to psoriasis, IL-17 pathway inhibitors (secukinumab and ixekizumab) have been shown to be effective in the treatment of PsA [141, 142].”

    From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [142]

  • In a laboratory model of multiple sclerosis, mice sensitized to myelin oligodendrocyte glycoprotein only developed experimental autoimmune encephalitis in the presence of commensal bacteria.

    “in a laboratory model of multiple sclerosis, mice sensitized to the autoantigen, myelin oligodendrocyte glycoprotein, only developed experimental autoimmune encephalitis in the presence of commensal bacteria.45”

    From The Gut Microbiome and the Brain (2014) · cites this paper as [45]

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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
Venue
Nature
Published
2011-10-26
Volume
479
Issue
7374
Pages
538-541
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
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
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 › Pathology and Forensic Medicine › 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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