Abstract
The success of corneal transplantation is limited by allograft rejection, but the pathogenic mechanisms of this disease remain poorly defined. In this study, we showed that the NOD, LRR-and pyrin domain-containing protein3 (NLRP3) inflammasome-mediated interleukin-1β (IL-1β) production exacerbated corneal allograft rejection. Extracellular ATP contributed to the NLRP3 inflammasome-mediated IL-1β release, which in turn was preferentially skewed toward Th17 differentiation via enhanced phosphorylation of STAT3. Pharmacological inhibition of IL-1β/IL-6-STAT3 signaling significantly delayed corneal allograft rejection. Thus, the identification of NLRP3 inflammasome's key role sheds new light on the pathogenesis of corneal allograft rejection and opens a potential new avenue for treating or preventing corneal allograft rejection.