TY - JOUR
T1 - Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination
AU - Berer, Kerstin
AU - Mues, Marsilius
AU - Koutrolos, Michail
AU - AlRasbi, Zakeya
AU - Boziki, Marina
AU - Johner, Caroline
AU - Wekerle, Hartmut
AU - Krishnamoorthy, Gurumoorthy
N1 - Funding Information:
Acknowledgements We thank I. Arnold-Ammer, N. Reißer and L. Penner for technical assistance, and M. Pfunder, U. Stauffer, C. Hornung and N. Joswig for maintaining our germ-free colony and technical support. We are much obliged to R. Kemler for his support. This work was funded by SFB 571 (Project B6), the German Competence Network on Multiple Sclerosis (KKNMS), ARSEP (France), and by the Max Planck Society. K.B. is supported by a fellowship from ARSEP. Z.A.R. is supported by a PhD fellowship from the Emirates Foundation. M.B. receives a fellowship from the Hellenic Neurological Society.
PY - 2011/11/24
Y1 - 2011/11/24
N2 - Active multiple sclerosis lesions show inflammatory changes suggestive of a combined attack by autoreactive T and B lymphocytes against brain white matter 1. 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 2. However, using the relapsing- remitting mouse model of spontaneously developing experimental autoimmune encephalomyelitis 3, 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.
AB - Active multiple sclerosis lesions show inflammatory changes suggestive of a combined attack by autoreactive T and B lymphocytes against brain white matter 1. 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 2. However, using the relapsing- remitting mouse model of spontaneously developing experimental autoimmune encephalomyelitis 3, 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.
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U2 - 10.1038/nature10554
DO - 10.1038/nature10554
M3 - Article
C2 - 22031325
AN - SCOPUS:81855167104
SN - 0028-0836
VL - 479
SP - 538
EP - 541
JO - Nature
JF - Nature
IS - 7374
ER -