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Samuel Hinshaw, Wambul (Sylvia) Wambul Wandu, Guangpu Shi, Jianfei Yang, Igal Gery; TMP778 Inhibits Induction of Experimental Autoimmune Uveitis and related immune responses. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):851.
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© ARVO (1962-2015); The Authors (2016-present)
TMP778, an inverse agonist of RORγt, was recently demonstrated to inhibit induction of experimental autoimmune disease (Xiao, et al., Immunity, 2014). Here, we determined the immunosuppressive property of TMP778 on the development of experimental autoimmune uveitis (EAU) and related immune responses.
Female B10.A mice immunized with an emulsion of interphotoreceptor retinoid-binding protein (IRBP) in complete Freund’s adjuvant (CFA) were treated twice daily with TMP778 (provided by Tempero Pharmaceuticals) by subcutaneous injection. Pathological changes in the eyes were determined by fundoscopy, while spleen cells were tested in vitro for cytokine production in response to IRBP. Separately, splenocytes from mice immunized with IRBP were cultured with TMP778 to test its inhibitory effect on the response to IRBP by cytokine release.
Fundoscopic analysis of the eyes showed that treatment of mice with TMP778 significantly inhibited the development of EAU (p ≤ 0.01). Furthermore, splenocytes from mice treated with TMP778 produced significantly less IFN-γ (p ≤ 0.001) and IL-17 (p ≤ 0.01) in response to IRBP than their controls. When added to cultures of splenocytes sensitized against IRBP, TMP778 strongly inhibited the release of IL-17. Additional data of ongoing studies are to be reported at the meeting.
Treatment of mice with TMP778 inhibits the development of EAU and cellular immune responses to IRBP. TMP778 and other inverse agonists of RORγt are a promising class of compounds for inhibition of immune-mediated disease.
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