Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis

Journal Article · Fri Jul 01 00:00:00 EDT 2016 · Investigative Opthalmology & Visual Science

DOI:https://doi.org/10.1167/iovs.16-19733· OSTI ID:1353349

Nakamura, Yukiko K. ^[1]; Metea, Christina ^[1]; Karstens, Lisa ^[2]; Asquith, Mark ^[3]; Gruner, Henry ^[1]; Moscibrocki, Cathleen ^[1]; Lee, Iris ^[1]; Brislawn, Colin J. ^[4]; Jansson, Janet K. ^[4]; Rosenbaum, James T. ^[5]; Lin, Phoebe ^[1]

---

1. Oregon Health and Science Univ., Portland, OR (United States). Casey Eye Inst.
2. Oregon Health and Science Univ., Portland, OR (United States). Dept. of Medical Informatics and Clinical Epidemiology
3. Oregon Health and Science Univ., Portland, OR (United States). Division of Rheumatology, Dept. of Medicine
4. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
5. Oregon Health and Science Univ., Portland, OR (United States). Casey Eye Inst.; Oregon Health and Science Univ., Portland, OR (United States). Division of Rheumatology, Dept. of Medicine; Devers Eye Inst., Portland, OR (United States)

The bacteria that live normally in our intestinal tract, or the gut microbiota contribute to the pathogenesis of extra intestinal autoimmune disease via their ability to dynamically educate the immune system. For example, in a mouse model of relapsing, remitting multiple sclerosis (MS), experimental autoimmune encephalomyelitis or EAE, several studies demonstrated that commensal microorganisms are essential in causing clinical disease activity. Interestingly, MS patients have a distinct gut microbiota to healthy controls. Several studies have also illustrated the importance of the gut microbiome in the development of other diseases, including Type 1 diabetes, metabolic syndrome, rheumatoid arthritis, and ankylosing spondylitis. Furthermore, HLA=B27 transgenic rats, which develop spontaneous spondyloarthropathy analogous to patients who have ankylosing spondylitis, associated with uveitis in humans, do not develop intestinal or peripheral join inflammation when raised in a germ-free environment. Our group has shown that HLA-B27 transgenic rats have an altered intestinal microbiota compared to healthy control rats. Given the similarities between the central nervous system (CNS) and the retina, as well as co-expression of potentially immunogenic self-antigens from the CNS and joint in the eye, we hypothesized that modulating the gut microbiome can result in amelioration of autoimmune uveitis. Although uveitis is a heterogeneous collection of diseases, in general immune-mediated, non-infectious, uveitis is thought to be due to a combination of genetic and environmental factors. It arises from an imbalance between the regulatory and effector arms of the immune system, result in an inappropriate immune reaction at an otherwise immune-privileged tissue site, the eye. Th1 and Th17 T lymphocytes are examples of effector immune cell subsets that my contribute to inflammatory disease of the eye, whereas regulatory T cells (Tregs) are an example of a regulatory immune cell subset that is typically required to downregulate an immune response to prevent uncontrolled disease. Experimental autoimmune uveitis (EAU) is a very robust, widely use model of T lymphoocyte mediated uveitis that can be induced in a certain strains of mice (e.g. B10.RIII) by immunizing these animals with a specific retinal antigen, interphotoreceptor binding protein (IRBP), but requires co-administration of an adjuvant containing killed Mycobacterium antigen. Lastly, this model of inducible uveitis is analogous to the EAE model of demyelinating disease mentioned above. EAU is a thought to be predominantly Th1 and Th17 mediated.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: National Institutes of Health (NIH); USDOE
• Grant/Contract Number: AC05-76RL01830
• OSTI ID: 1353349
• Report Number(s): PNNL-SA--117611
• Journal Information: Investigative Opthalmology & Visual Science, Journal Name: Investigative Opthalmology & Visual Science Journal Issue: 8 Vol. 57; ISSN 1552-5783
• Publisher: Association for Research in Vision and Ophthalmology
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
antibiotics
autoimmune uveitis
microbial
microbiome
regulatory T cells
uveitis