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Cell. 2018 Dec 21. pii: S0092-8674(18)31560-5. doi: 10.1016/j.cell.2018.11.035. [Epub ahead of print]

Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10.

Author information

1
Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
2
Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
3
Neuroimmunology Unit, CRCHUM and Department of Neurosciences, Faculty of Medicine, Université de Montréal, QC H2X 0A9, Canada.
4
University of Melbourne, School of Biomedical Sciences, Parkville, VIC 3010, Australia.
5
Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto General Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada.
6
Toronto General Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada; Department of Laboratory and Medicine Pathology, University of Toronto, Toronto, ON M5S 1A8, Canada.
7
Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
8
Benaroya Research Institute and Department of Immunology University of Washington School of Medicine, Seattle, WA 98101, USA.
9
Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
10
Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada.
11
Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka Prefecture 584-8540, Japan.
12
Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Program in Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
13
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
14
Department of Laboratory and Medicine Pathology, University of Toronto, Toronto, ON M5S 1A8, Canada.
15
Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto General Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada; Department of Laboratory and Medicine Pathology, University of Toronto, Toronto, ON M5S 1A8, Canada.
16
Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA; Graduate Program in Bioinformatics, University of California, San Francisco, San Francisco, CA 94143, USA.
17
Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: jen.gommerman@utoronto.ca.

Abstract

Plasma cells (PC) are found in the CNS of multiple sclerosis (MS) patients, yet their source and role in MS remains unclear. We find that some PC in the CNS of mice with experimental autoimmune encephalomyelitis (EAE) originate in the gut and produce immunoglobulin A (IgA). Moreover, we show that IgA+ PC are dramatically reduced in the gut during EAE, and likewise, a reduction in IgA-bound fecal bacteria is seen in MS patients during disease relapse. Removal of plasmablast (PB) plus PC resulted in exacerbated EAE that was normalized by the introduction of gut-derived IgA+ PC. Furthermore, mice with an over-abundance of IgA+ PB and/or PC were specifically resistant to the effector stage of EAE, and expression of interleukin (IL)-10 by PB plus PC was necessary and sufficient to confer resistance. Our data show that IgA+ PB and/or PC mobilized from the gut play an unexpected role in suppressing neuroinflammation.

KEYWORDS:

B cells; EAE; IgA; MS; experimental autoimmune encephalomyelitis; microbiota; multiple sclerosis; plasma cells; small intestinal lamina propria

PMID:
30612739
DOI:
10.1016/j.cell.2018.11.035

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