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

First Author  Rojas OL Year  2019
Journal  Cell Volume  176
Issue  3 Pages  610-624.e18
PubMed ID  30612739 Mgi Jnum  J:294855
Mgi Id  MGI:6458860 Doi  10.1016/j.cell.2018.11.035
Citation  Rojas OL, et al. (2019) Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10. Cell 176(3):610-624.e18
abstractText  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.
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