The NLRP3 inflammasome regulates corneal allograft rejection through enhanced phosphorylation of STAT3

  • Am J Transplant. 2020 Dec;20(12):3354-3366. doi: 10.1111/ajt.16071.
Chao Wei  1 ,  Li Ma  1 ,  Hao Chi  1  2 ,  Lin Li  1 ,  Sai Zhang  1  2 ,  Wenhui Yin  1  3 ,  Ting Liu  1 ,  Hua Gao  1 ,  Weiyun Shi  1
Affiliations
  • 1. State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China.
  • 2. School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, China.
  • 3. Department of Medicine, Qingdao University, Qingdao, China.
PMID: 32583615 DOI: 10.1111/ajt.16071
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.

Keywords
basic (laboratory) research; cytokine receptors, animal models: murine; immune modulation, rejection: acute, innate immunity, immune regulation, cytokines; ophthalmology, immunosuppression; science, corneal transplantation; science, translational research.
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