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Chao Wei, Demeng Xiang, Li Ma, Hua Gao, Weiyun Shi; NLRP3 inflammasome regulates acute corneal allograft rejection through enhanced phosphorylation of STAT3. Invest. Ophthalmol. Vis. Sci. 2019;60(9):894.
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© ARVO (1962-2015); The Authors (2016-present)
Accumulative evidence indicated the involvement of NLRP3 inflammasome in the pathogenesis of allograft rejection. However, its contribution to corneal allograft rejection remains unknown. Here we investigate the effect of NLRP3 inflammasome on corneal allograft rejection.
Orthotopic corneal transplantation was performed to assess the effects of IL-1β blockade via neutralizing antibody, as well as the effects of NLRP3 inflammasome using genetical and pharmacological approaches. Grafts were evaluated by ophthalmic slit-lamp biomicroscopy for one month and analyzed by Kaplan-Meier survival curve. The pathological changes were examined using HE staining, real-time PCR and ELISA. Additionally, the effect of NLRP3 inflammasome on Th17 cells was investigated by flow cytometry and western blot, respectively.
Blockade of IL-1β signaling using neutralizing antibody significantly improved the survival of corneal allografts. The NLRP3 inflammasome component Nlrp3, which is required for pro-IL-1β maturation, was critical for the pathogenesis of corneal allograft rejection. Extracellular ATP contributed to NLRP3 inflammasome-mediated IL-1β production, and inhibition of ATP/P2X7 signaling pharmacologically not only pronouncedly prolonged the survival of corneal allografts but also decreased the IL-1β production. Mechanistically, NLRP3 inflammasome derived IL-1β promoted Th17 responses through enhanced STAT3 phosphorylation. Furthermore, both blockade of STAT3 signaling pharmacologically and IL-17 signaling via neutralizing antibody significantly delayed the pathogenesis of corneal allograft rejection.
NLRP3 inflammasome promoted corneal allograft rejection through Th17 responses induced by enhanced STAT3 phosphorylation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
NLRP3 inflammasome promoted corneal allograft rejection.
NLRP3 infalmmasome promoted corneal allograft rejection through Th17 response induced by enhanced STAT3 phosphorylation
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