NKT cell-dependent amelioration of a mouse model of multiple sclerosis by altering gut flora.
Improved hygiene has been suggested to influence certain autoimmune disorders, such as multiple sclerosis. In this study, we addressed whether altering the composition of gut flora may affect susceptibility to experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We administered a mixture of non-absorbing antibiotics, kanamycin, colistin, and vancomycin (KCV), orally to mice induced to develop EAE. The antibiotic treatment, beginning 1 week prior to sensitization, altered the composition of gut flora and, intriguingly, also ameliorated the development of EAE. While this result was associated with a reduced production of pro-inflammatory cytokines from the draining lymph node cells, a reduction of mesenteric Th17 cells was found to correlate with disease suppression. In addition, we found that Valpha14 invariant NKT (iNKT) cells were necessary for maintaining the mesenteric Th17 cells. The homologous effects of KCV treatment and iNKT cell depletion led us to speculate that KCV treatment may suppress EAE by altering the function of iNKT cells. Consistent with this hypothesis, KCV treatment did not suppress EAE that was induced in iNKT cell-deficient mice, although it was efficacious in mice that lacked Valpha19 mucosal-associated invariant T cells. Thus, gut flora may influence the development of EAE in a way that is dependent on iNKT cells, which has significant implications for the prevention and treatment of autoimmune diseases.
Yokote
Hiroaki
H
Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Miyake
Sachiko
S
Croxford
J Ludovic
JL
Oki
Shinji
S
Mizusawa
Hidehiro
H
Yamamura
Takashi
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology*; D020381:Interleukin-17 / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology; D055611:Natural Killer T-Cells / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D018949:Antigens, CD1; D016207:Cytokines; D020381:Interleukin-17; D001613:beta 2-Microglobulin