Microbiota as Drivers and as Therapeutic Targets in Ocular and Tissue Specific Autoimmunity

Autoimmune uveitis is a major cause of blindness in humans. Activation of retina-specific autoreactive T cells by commensal microbiota has been shown to trigger uveitis in mice. Although a culprit microbe and/or its immunogenic antigen remains to be identified, studies from inducible and spontaneous mouse models suggest the potential of microbiota-modulating therapies for treating ocular autoimmune disease. In this review, we summarize recent findings on the contribution of microbiota to T cell-driven, tissue-specific autoimmunity, with an emphasis on autoimmune uveitis, and analyze microbiota-altering interventions, including antibiotics, probiotics, and microbiota-derived metabolites (e.g., short-chain fatty acids), which have been shown to be effective in other autoimmune diseases. We also discuss the need to explore more translational animal models as well as to integrate various datasets (microbiomic, transcriptomic, proteomic, metabolomic, and other cellular measurements) to gain a better understanding of how microbiota can directly or indirectly modulate the immune system and contribute to the onset of disease. It is hoped that deeper understanding of these interactions may lead to more effective treatment interventions.