Darren J. Lee, PhD
- Autoimmune uveitis and the mechanisms that provide resistance to relapse
- Understanding how ocular derived regulatory T cells function to provide resistance to autoimmune disease
- Identification of novel mechanisms to induce suppressor macrophages and regulatory T cells
- B.S. in Genetics, University of California, Davis, CA
- Ph.D. in Genetics, University of New Hampshire, Durham, NH
- Postdoctoral Training, Harvard Medical School, Schepens Eye Research Institute, Boston, MA
- Postdoctoral Training, Boston University School of Medicine, Boston, MA
- Uveitis is a debilitating and potentially blinding inflammatory disease that affects 93 in 100,000 Americans annually. The current treatment strategy is to control the inflammation with immunosuppressive medication that include steroids, which in turn have serious side effects, such as cataracts, glaucoma, peptic ulcers, bone decalcification, and systemic susceptibility to infection.
- A mouse model of human autoimmune uveitis, experimental autoimmune uveitis (EAU) has been used to better understand this disease. In contrast to chronic human uveitis, EAU resolves without intervention and mice are resistant to recrudescence of uveitis because of regulatory immunity found in the spleen. This regulatory immunity requires post-EAU Treg cells to be activated by post-EAU antigen presenting cells (APC). We have shown that the melanocortin 5 receptor (MC5r) is required for the emergence of a suppressive APC in the post-EAU spleen, and this APC is a source of adenosine that activates the post-EAU Treg cell through the adenosine 2A receptor (A2Ar). This is an interesting finding, because these two pathways have been shown to individually regulate immunity, but our observation is the first to link the two pathways. The result of stimulating this melanocortin-adenosinergic pathway is an autoantigen specific Treg cell that suppresses EAU.
- My focus is how these Treg cells function to suppress inflammation, the intracellular signaling pathway that occur in the suppressor APC upon MC5r stimulation, and to determine if MC5r or A2Ar stimulation is effective in the promotion of regulatory activity in uveitis patients.