1. Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10
- Author
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Arthur Mortha, Sergio E. Baranzini, Ghazal Najafi, Georgina Galicia, Daniel A. Winer, Khashayar Khaleghi, Daniel J. Campbell, Dennis S. W. Lee, Helen Luck, Eric Y. Cao, Leslie Y. T. Leung, Clinton S. Robbins, Angela A. Wang, Alexandre Prat, Marc S. Horwitz, Scott S. Zamvil, Lesley A. Ward, Michio Tomura, Pailin Chiaranunt, Tian Sun, Anne-Katrin Pröbstel, Olga L. Rojas, Kyle Burrows, Lisa C. Osborne, Angela Li, Hannah G. Robinson, David Allman, Beatriz Garcillán, Jennifer Y. Yam, Jessica R. Allanach, Jennifer L. Gommerman, Fabienne Mackay, Ikbel Naouar, Valeria Ramaglia, David G. Brooks, Rickvinder Besla, Marc Charabati, Elisa A. Porfilio, Ryan Baumann, and Amit Bar-Or
- Subjects
Immunoglobulin A ,Encephalomyelitis ,experimental autoimmune encephalomyelitis ,Neurodegenerative ,Inbred C57BL ,Medical and Health Sciences ,Atacicept ,Mice ,0302 clinical medicine ,Intestinal mucosa ,Intestinal Mucosa ,0303 health sciences ,EAE ,Experimental autoimmune encephalomyelitis ,Interleukin ,Biological Sciences ,Interleukin-10 ,3. Good health ,Intestines ,Interleukin 10 ,IgA ,Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,Neuroimmunomodulation ,Plasma Cells ,Biology ,Autoimmune Disease ,Article ,General Biochemistry, Genetics and Molecular Biology ,Experimental ,03 medical and health sciences ,microbiota ,medicine ,Animals ,Humans ,Neuroinflammation ,030304 developmental biology ,B cells ,Neurosciences ,MS ,medicine.disease ,Brain Disorders ,Mice, Inbred C57BL ,Immunology ,biology.protein ,Digestive Diseases ,small intestinal lamina propria ,030217 neurology & neurosurgery ,Autoimmune ,Developmental Biology - 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) and/or 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 and/or 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.
- Published
- 2019
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