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Lin Sun, Xinyi Wu; TSLP-activated dendritic cells induce T helper type 2 inflammation in Aspergillusfumigatus keratitis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):495.
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Corneal epithelial cells can, under the stimulation of A. fumigatus, up-regulate secretion of thymic stromal lymphopoietin (TSLP) and enhance innate immunity. TSLP can increase the proliferation of CD4+T cells, and inducing Th2 inflammation to participate in adaptive immunity. DCs may be related to this process. We want to explore whether DCs have participated in this process, and if DCs do, what role they have played in such process.
We subconjunctivally injected the mouse eyes with TSLP siRNA and rTSLP, infected the mice with a fungal conidia suspension. Mice with phosphate buffer saline were used as the negative control. Mice with no treatment were used as the blank control. We measured the proliferation, maturation, and migration of CD11c+DCs, and evaluated expression of Th2-attracting chemokines, proinflammatory cytokine and Th2 cytokines.
We demonstrated that in A. fumigatus-infected corneas, DCs proliferated, matured, and gradually migrated not only from the basement membrane to the corneal epithelium, but also from the corneal limbus to the central cornea. Mature DCs secreted Th2-attracting chemokines, the thymus and activation-regulated chemokine (TARC), and the macrophage-derived chemokine (MDC), encouraging the secretion of TNF-α and Th2 cytokine Interleukin (IL) -4, IL-5, and IL-13. The above processes were all restricted with subconjunctivally injection of TSLP siRNA, while they were strengthened with the injection of rTSLP. All the experimental results were statistically significant. Bars: mean ± SD of three independent experiments. *P < 0.05.
Our study demonstrated that in A. fumigatus keratitis, TSLP promotes the proliferation, maturation and migration of DCs, while mature DCs secrete Th2-attracting chemokines TARC and MDC, promoting the secretion of proinflammatory cytokine TNF-α and Th2 cytokines IL-4, IL-5 and IL-13 to trigger Th2-dominant inflammation. Our study may provide new thinking and a target for the treatment of fungal keratitis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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