Autoimmunity

RESEARCH HIGHLIGHTS

Nature Reviews Immunology | AOP, published online 11 November 2011; doi:10.1038/nri3114

AUTOIMMUNITY Linking commensals with autoimmunity Autoimmune disorders develop myelin oligodendrocyte glycoprotein commensal bacteria in the gut and under the combined influence of (MOG). As disease incidence in the subsequent proliferation of these both environmental and genetic factors. these transgenic mice varies among T cells. commensal A recent study published in Nature different animal facilities, the authors In addition to the increased + bacteria and reports that both commensal bacteria asked whether the composition of the activation of autoreactive CD4 and self-antigen recognition are intestinal microbiota might have a T cells, B cells are crucial for disease self-antigen required for the initiation of auto role in EAE development. development. Serum from SPF trans- recognition are immune responses in relapsing– Indeed, whereas 80% of the transgenic mice contained higher levels of required for remitting experimental autoimmune genic mice housed under specific MOG-specific IgG2a antibodies than the initiation encephalomyelitis (EAE), a mouse pathogen-free (SPF) conditions serum from germ-free transgenic model of multiple sclerosis. developed EAE, transgenic mice mice. However, the induction of of autoimmune The intestinal microbiota actively housed under germ-free conditions MOG-specific B cell responses in responses regulates local immune responses, showed no disease symptoms. This SPF transgenic mice did not rely on partly through the induction of effect was not due to differential molecular mimicry between MOG interleukin‑17 (IL‑17)-producing maturation of the immune system, epitopes and epitopes provided by T cells and regulatory T cells, but its as active immunization with recom- commensal bacteria, but was depend- contribution to immune responses binant MOG induced autoimmune ent on self-antigen expression, as at distal sites is largely unknown. responses in the transgenic mice MOG-specific autoantibodies were Relapsing–remitting EAE develops irrespective of the presence of the absent from SPF transgenic mice that spontaneously in transgenic mice intestinal microbiota. Moreover, were deficient for MOG. of the SJL/J background in which colonization of germ-free transgenic Interestingly, the cervical a proportion of CD4+ T cells are mice with commensal bacteria was lymph nodes of young, healthy SPF engineered to express a T cell recep- sufficient for EAE development. transgenic mice contained germinal tor that is specific for the self antigen Further analysis indicated that, centres and germinal centre B cells. in accordance with previous findings, This was not observed in germ-free the percentage of IL‑17‑producing transgenic mice or SPF wild-type CD4+ T cells in the lamina propria mice, indicating that autoreactive and Peyer’s patches was higher in T cells previously activated by SPF transgenic mice than in germ- commensal bacteria initiate MOG- free transgenic mice. Moreover, specific germinal centre reactions splenic T cells from SPF transgenic in a MOG-dependent manner. The mice produced higher levels of elucidation of the compositions of interferon-γ and IL‑17 in vitro than intestinal microbiota that result in splenic T cells from germ-free trans- increased susceptibility to auto genic mice. Finally, adoptively immunity through this mechanism transferred MOG-specific or will be of therapeutic value. polyclonal CD4+ T cells were shown Maria Papatriantafyllou to proliferate locally in the lamina propria of SPF mice, and antibiotic ORIGINAL RESEARCH PAPER Berer, K. et al. treatment abolished this effect. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Together, these findings indicate Nature 26 Oct 2011 (doi:10.1038/nature10554) that a first step in the initiation of FURTHER READING Gill, N. & Finlay, B. B. The gut autoimmunity might be the activa- microbiota: challenging immunology. Nature Rev. Immunol. 11, 636–637 (2011) tion of autoreactive CD4+ T cells by