The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination
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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“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 the citing paper
“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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Cites
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Cited by
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Role of the microbiota in immunity and inflammation.
Belkaid, Y., & Hand, T. W. (2014) · Cell · doi:10.1016/j.cell.2014.03.011 · Cited by 5,385
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Cryan, J. F., & Dinan, T. G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3346 · Cited by 4,572
Host microbiota constantly control maturation and function of microglia in the CNS
Erny, D., Hrabě de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4030 · Cited by 3,569
Gut microbiota, metabolites and host immunity
Rooks, M. G., & Garrett, W. S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.42 · Cited by 3,409
Metadata
- 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
- 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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