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Cuiyan Tan, Francoise Meylan, Barbara Vistica, Richard Siegel, Igal Gery; TL1A is a potent enhancer of IL-9 production and ocular immunopathogenicity by Th9 cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):354.
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IL-9 is a cytokine that plays a major role in the immune response against helminths and in the pathogenic processes of allergy and inflammation. A subpopulation of T-helper cells, designated “Th9”, that selectively produce IL-9, mediates inflammation in mouse eyes expressing the target antigen. TL1A (also known as TNFSF15), a tumor necrosis factor (TNF) family member, co-stimulates T cells and enhances their proliferative responses through its receptor DR3 (TNFRSF25). This study examined the capacity of TL1A to promote the generation of Th9 cells and to enhance their ocular immunopathogenicity.
Naïve CD4 cells expressing TCR specific against hen egg lysozyme (HEL) were incubated with HEL and Th9-inducing cytokines, with or without TL1A and their production of IL-9 and IL-10 was determined by flow cytometry, qPCR and ELISA. The immunopathogenicity of Th9 cells was assessed by their capacity to induce inflammation in recipient eyes expressing HEL. The local effect of TL1A was tested by intraocular injection of the molecule into recipient of Th9 cells, whereas anti-TL1A antibodies were injected into Th9 recipients to determine their inhibitory effect on the disease severity.
TL1A enhanced the generation of Th9 in culture, increasing the proportion of IL-9 producing cells from ~40% to ~90%, while reducing the proportion of IL-10 producing Th9 cells from ~22% to ~2%. Importantly, Th9 cells generated in the presence of TL1A were more efficient than their controls in inducing ocular inflammation. Intraocular administration of TL1A increased moderately the Th9-induced ocular inflammation, whereas systemic treatment with anti-TL1A antibodies reduced significantly the Th9-induced ocular inflammation.
The cytokine TL1A profoundly promotes Th9 differentiation and pathogenicity and might be a therapeutic target in ocular and other immune-mediated diseases.
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