Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination.
Active multiple sclerosis lesions show inflammatory changes suggestive of a combined attack by autoreactive T and B lymphocytes against brain white matter. These pathogenic immune cells derive from progenitors that are normal, innocuous components of the healthy immune repertoire but become autoaggressive upon pathological activation. The stimuli triggering this autoimmune conversion have been commonly attributed to environmental factors, in particular microbial infection. However, using the relapsing-remitting mouse model of spontaneously developing experimental autoimmune encephalomyelitis, here we show that the commensal gut flora-in the absence of pathogenic agents-is essential in triggering immune processes, leading to a relapsing-remitting autoimmune disease driven by myelin-specific CD4(+) T cells. We show further that recruitment and activation of autoantibody-producing B cells from the endogenous immune repertoire depends on availability of the target autoantigen, myelin oligodendrocyte glycoprotein (MOG), and commensal microbiota. Our observations identify a sequence of events triggering organ-specific autoimmune disease and these processes may offer novel therapeutic targets.
Department of Neuroimmunology, Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.
Kerstin
K
Berer
Marsilius
M
Mues
Michail
M
Koutrolos
Zakeya Al
ZA
Rasbi
Marina
M
Boziki
Caroline
C
Johner
Hartmut
H
Wekerle
Gurumoorthy
G
Krishnamoorthy
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology; D002465:Cell Movement; D016207:Cytokines / Q000276:immunology; D004032:Diet; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000382:microbiology; D005856:Germ-Free Life / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D054892:Metagenome / Q000276:immunology*; D051379:Mice; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D009185:Myelin Proteins / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology* / Q000473:pathology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D013270:Stomach / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology
D001324:Autoantigens; D016207:Cytokines; C571327:Mog protein, mouse; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein