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Immunity. 2015 Aug 18;43(2):343-53. doi: 10.1016/j.immuni.2015.07.014.

Microbiota-Dependent Activation of an Autoreactive T Cell Receptor Provokes Autoimmunity in an Immunologically Privileged Site.

Author information

1
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892, USA.
2
Oral and Pharyngeal Cancer Branch, National Institutes of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA.
3
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892, USA; State Key of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
4
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
5
Keio University School of Medicine, Tokyo 160-8582, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
6
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892, USA. Electronic address: caspir@mail.nih.gov.

Abstract

Activated retina-specific T cells that have acquired the ability to break through the blood-retinal barrier are thought to be causally involved in autoimmune uveitis, a major cause of human blindness. It is unclear where these autoreactive T cells first become activated, given that their cognate antigens are sequestered within the immune-privileged eye. We demonstrate in a novel mouse model of spontaneous uveitis that activation of retina-specific T cells is dependent on gut commensal microbiota. Retina-specific T cell activation involved signaling through the autoreactive T cell receptor (TCR) in response to non-cognate antigen in the intestine and was independent of the endogenous retinal autoantigen. Our findings not only have implications for the etiology of human uveitis, but also raise the possibility that activation of autoreactive TCRs by commensal microbes might be a more common trigger of autoimmune diseases than is currently appreciated.

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PMID:
26287682
PMCID:
PMC4544742
DOI:
10.1016/j.immuni.2015.07.014
[Indexed for MEDLINE]
Free PMC Article

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