Journal article

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

Olga L Rojas, Anne-Katrin Probstel, Elisa A Porfilio, Angela A Wang, Marc Charabati, Tian Sun, Dennis SW Lee, Georgina Galicia, Valeria Ramaglia, Lesley A Ward, Leslie YT Leung, Ghazal Najafi, Khashayar Khaleghi, Beatriz Garcillan, Angela Li, Rickvinder Besla, Ikbel Naouar, Eric Y Cao, Pailin Chiaranunt, Kyle Burrows Show all

Cell | CELL PRESS | Published : 2019

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 EA..

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University of Melbourne Researchers

Grants

Awarded by Canadian Institutes of Health Research


Awarded by Swiss National Science Foundation fellowship


Awarded by National Multiple Sclerosis Society fellowship (NMSS Kathleen C. Moore Fellowship)


Awarded by NIH


Awarded by Canadian Institutes of Health Research (CIHR) Foundation


Awarded by NMSS


Awarded by US National MS Society


Awarded by US Department of Defense


Awarded by CIHR Foundation grant


Awarded by MS Society of Canada grant


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

We would like to acknowledge Dr. Andy Luster for sending us the Kaede mice, with permission from Drs. Yoshihiro Miwa and Tomura Kanagawa and permission from Dr. Casey Weaver to use 10BiT mice. We also thank Dr. Rafael Casellas for AID-YFP mice and Dr. Harry Greenberg for kindly providing the EC Rotavirus. We are grateful for the expertise of Dionne White in the Faculty of Medicine Flow Cytometry facility and for our colleagues in the Faculty of Medicine Division of Comparative Medicine for assistance with EAE experiments. We would like to acknowledge Dr. Bruce Cree, Dr. Jennifer Graves and Sneha Singh for patient recruitment and Drs. Xiaoyuan Zhou and Chris Graham Fenton for computational expertise. A. M. is supported by an Operating Grant from the Canadian Institutes of Health Research (CIHR 388337) and is the Tier 2 Canadian Research Chair in Mucosal Immunology. J.L.G., A.B.-O., and A.P. are supported by a collaborative team grant ("B cells in MS'') from the MS Society of Canada Research Foundation, and A.P. is also supported by a Tier 1 Canada Research Chair in Multiple Sclerosis. A.-K.P. is supported by a Swiss National Science Foundation fellowship (P2SKP3_164938/1 and P300PB_177927/1) and a National Multiple Sclerosis Society fellowship (NMSS Kathleen C. Moore Fellowship: FG-1708-28871). D.A. is supported by NIH (R01-AI113543). D.G.B. receives funding from the Canadian Institutes of Health Research (CIHR) Foundation Grant (FDN148386) and from NIH (AI085043SSZ). S.S.Z. receives research receives funding from the NIH (RO1 NS092835 and R21 NS108159-01), the NMSS (RG1701-26628), The Maisin Foundation, Biogen, and Celgene. S.E.B. holds the Heidrich Family and Friends endowed Chair in Neurology at UCSF and is supported by the US National MS Society (CA1072-A-7), the US Department of Defense (W81XWH-15-1-0652), and the Valhalla Charitable Foundation. J.L.G.'s lab is supported by a CIHR Foundation grant (FDN1552) and an MS Society of Canada grant (EGID3194).