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

Cell. 2019 Jan 24;176(3):610-624.e18. doi: 10.1016/j.cell.2018.11.035. Epub 2019 Jan 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin A / metabolism*
  • Interleukin-10 / metabolism*
  • Intestinal Mucosa / metabolism
  • Intestines / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / immunology
  • Neuroimmunomodulation / immunology
  • Plasma Cells / metabolism


  • Immunoglobulin A
  • Interleukin-10