@article{a6e49b0499af4b4d91f30b828b4aa017,
title = "MaDCAM-1-mediated intestinal lymphocyte homing is critical for the development of active experimental autoimmune encephalomyelitis",
abstract = "Lymphocyte homing into the intestine is mediated by binding of leukocytes to mucosal addressin cell adhesion molecule 1 (MAdCAM-1), expressed on endothelial cells. Currently, the immune system of the gut is considered a major modulator not only of inflammatory bowel disease, but also of extra-intestinal autoimmune disorders, including multiple sclerosis (MS). Despite intense research in this field, the exact role of the intestine in the pathogenesis of (neuro-)inflammatory disease conditions remains to be clarified. This prompted us to investigate the role of MAdCAM-1 in immunological processes in the intestine during T cell-mediated autoimmunity of the central nervous system (CNS). Using the experimental autoimmune encephalomyelitis model of MS, we show that MAdCAM-1-deficient (MAdCAM-1-KO) mice are less susceptible to actively MOG35−55-induced disease. Protection from disease was accompanied by decreased numbers of immune cells in the lamina propria and Peyer's patches as well as reduced immune cell infiltration into the spinal cord. MOG35−55-recall responses were intact in other secondary lymphoid organs of MAdCAM-1-KO mice. The composition of specific bacterial groups within the microbiome did not differ between MAdCAM-1-KO mice and controls, while MAdCAM-1-deficiency severely impaired migration of MOG35−55-activated lymphocytes to the gut. Our data indicate a critical role of MAdCAM-1 in the development of CNS inflammation by regulating lymphocyte homing to the intestine, and may suggest a role for the intestinal tract in educating lymphocytes to become encephalitogenic.",
keywords = "EAE/MS, Intestine, Lymphocyte homing, MAdCAM-1, Neuroinflammation",
author = "Kristina Kuhbandner and Anna Hammer and Stefanie Haase and Elisa Terbrack and Alana Hoffmann and Angela Schippers and Norbert Wagner and Hussain, {Rehana Z.} and Miller-Little, {William A.} and Koh, {Andrew Y.} and Stoolman, {Joshua S.} and Segal, {Benjamin M.} and Linker, {Ralf A.} and Olaf St{\"u}ve",
note = "Funding Information: Conflict of Interest Statement: OS serves on the editorial boards of the Multiple Sclerosis Journal, and Therapeutic Advances in Neurological Disorders and has served on data monitoring committees for Pfizer and TG Therapeutics without monetary compensation. OS has advised EMD Serono and Genzyme and currently receives grant support from Sanofi Genzyme. OS received travel support from Shire. RL received compensation for activities with Bayer, Biogen, Genzyme, Merck, Novartis, Roche, and TEVA as well as research support from Biogen and Novartis. Funding Information: OS was supported by a visting professorship from the IZKF Erlangen, Germany and parts of the study were funded by Roberta I. and Norman L. Pollock Fund (AK). Funding Information: We are grateful to Silvia Seubert for expert technical assistance. KK and AlH are graduate students of the research training group 2162 Neurodevelopment and Vulnerability of the Central Nervous System of the Deutsche Forschungsgemeinschaft (DFG GRK2162). RL is a member of the research training group 2162 of the Deutsche Forschungsgemeinschaft (DFG GRK2162). AS and NW were funded by the Deutsche Forschungsgemeinschaft (SCHI 1170/2-1 and WA 1127/4-1). This work was supported by the Interdisciplinary Center for Clinical Research (IZKF Erlangen, TP E24). KK was a graduate student of the IZKF Erlangen. Publisher Copyright: Copyright {\textcopyright} 2019 Kuhbandner, Hammer, Haase, Terbrack, Hoffmann, Schippers, Wagner, Hussain, Miller-Little, Koh, Stoolman, Segal, Linker and St{\"u}ve.",
year = "2019",
doi = "10.3389/fimmu.2019.00903",
language = "English (US)",
volume = "10",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "APR",
}