Experimental Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Invest Ophthalmol Vis Sci. 2013 Nov 13;54(12):7463-9. doi: 10.1167/iovs.12-11479.
Ligands for aryl hydrocarbon receptor (AHR), such as dioxins, are highly toxic. One such ligand, TCDD, was found to exert potent immunosuppressive capacities in mice developing pathogenic autoimmune processes, including EAU, but its toxicity makes it unusable for humans. A recently identified endogenous AHR ligand, ITE, is also immunosuppressive, but is nontoxic and could therefore be useful for therapy in humans. Here, we tested ITE for its capacity to inhibit EAU and related immune responses.
EAU was induced in B10.A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP; 40 μg) in CFA. Treatment with ITE was by daily intraperitoneal injection of 0.2 mg. Disease severity was assessed by both fundoscopy and histological examination. Draining lymph node cells were tested for proliferation by thymidine uptake and for cytokine production and release by ELISA. In addition, the intracellular expression of cytokines and Foxp3 was determined by flow cytometry. Serum antibodies were measured by ELISA.
Treatment with ITE efficiently inhibited the development of EAU in mice, as well as the cellular immune responses against IRBP and PPD. ITE treatment inhibited the expansion of both Th1 and Th17 subpopulations, as well as their release of the signature cytokines, IFN-gamma and IL-17. The treatment moderately increased, however, the proportion of Foxp3 expressing T-regulatory cells. Antibody production was not affected by the treatment.
ITE, an endogenous AHR ligand, efficiently inhibits EAU development and related cellular immune responses. Being nontoxic, ITE may be considered for treatment of pathogenic immunity in humans.
芳基烃受体（AHR）的配体，如二恶英，具有很强的毒性。一种这样的配体，TCDD，在发展致病自身免疫过程的小鼠中发现具有很强的免疫抑制能力，包括 EAU，但它的毒性使其不能用于人类。最近发现的内源性 AHR 配体，ITE，也是免疫抑制的，但没有毒性，因此可用于人类治疗。在这里，我们测试了 ITE 抑制 EAU 和相关免疫反应的能力。
通过用 CFA 中的视黄醇结合蛋白（IRBP；40μg）免疫 B10.A 小鼠来诱导 EAU。ITE 的治疗方法是每天腹腔注射 0.2mg。通过眼底镜检查和组织学检查评估疾病严重程度。通过胸苷摄取测试和 ELISA 测试检测引流淋巴结细胞的增殖和细胞因子的产生和释放。此外，通过流式细胞术确定细胞内细胞因子和 Foxp3 的表达。通过 ELISA 测量血清抗体。
ITE 治疗有效地抑制了 EAU 在小鼠中的发展，以及针对 IRBP 和 PPD 的细胞免疫反应。ITE 治疗抑制了 Th1 和 Th17 亚群的扩增，以及它们释放特征细胞因子 IFN-γ和 IL-17。然而，该治疗适度增加了表达 Foxp3 的 T 调节细胞的比例。治疗未影响抗体产生。
ITE，一种内源性 AHR 配体，有效地抑制 EAU 的发展和相关的细胞免疫反应。ITE 没有毒性，可考虑用于治疗人类的致病性免疫。
