| Literature DB >> 30612739 |
Olga L Rojas1, Anne-Katrin Pröbstel2, Elisa A Porfilio1, Angela A Wang1, Marc Charabati3, Tian Sun1, Dennis S W Lee1, Georgina Galicia1, Valeria Ramaglia1, Lesley A Ward1, Leslie Y T Leung1, Ghazal Najafi1, Khashayar Khaleghi1, Beatriz Garcillán4, Angela Li5, Rickvinder Besla6, Ikbel Naouar1, Eric Y Cao1, Pailin Chiaranunt1, Kyle Burrows1, Hannah G Robinson7, Jessica R Allanach7, Jennifer Yam1, Helen Luck5, Daniel J Campbell8, David Allman9, David G Brooks10, Michio Tomura11, Ryan Baumann2, Scott S Zamvil12, Amit Bar-Or13, Marc S Horwitz14, Daniel A Winer6, Arthur Mortha1, Fabienne Mackay4, Alexandre Prat3, Lisa C Osborne7, Clinton Robbins15, Sergio E Baranzini16, Jennifer L Gommerman17.
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.Entities:
Keywords: B cells; EAE; IgA; MS; experimental autoimmune encephalomyelitis; microbiota; multiple sclerosis; plasma cells; small intestinal lamina propria
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Year: 2019 PMID： 30612739 PMCID： PMC6903689 DOI： 10.1016/j.cell.2018.11.035
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582