Basic and Translational Science Posters

Tuesday July 03, 2018 from 16:30 to 17:30

Room: Hall 10 - Exhibition

P.458 CD137L signaling is an inflammation checkpoint in renal inflammation

Jong Soo Lee, Korea

Professor
Division of Nephroy
Ulsan University Hospital

Abstract

CD137L Signaling is an Inflammation Checkpoint in Renal Inflammation

Jong Soo Lee1,3, Hong Rae cho2,3, Byungsuk Kwon3,4, Kyung Sun Park1,3, Juyang Kim3,4, Hyejung Kim3,4, Sangjoon Park2,3.

1Internal Medicine, Ulsan University Hospital, College of Medicine, Ulsan, Korea; 2Surgery, Ulsan University Hospital, College of Medicine, Ulsan, Korea; 3Biomedical Research Center, Ulsan University Hospital, College of Medicine, Ulsan, Korea; 4School of Bilogical Sciences, University of Ulsan, Ulsan, Korea

We have previously shown that signaling via CD137 ligand (CD137L) promotes renal inflammation occurring after ischemia-reperfusion injury by inducing production of neutrophil-recruiting chemokines from tubular epithelial cells. In this study, we provide evidence showing that CD137L signaling enhances resolution of renal inflammation and renal tissue repair. Administration of CD137-Fc fusion protein 24 hours after renal ischemia-reperfusion injury increased Arginase-expressing macrophages and proliferation of tubular epithelial cells. RNA seq analysis of bone marrow-derived macrophages (BMDMs) showed decreased expression of inflammatory genes and increased expression of anti-inflammatory genes. Interestingly, GM-CSF and CD137-Fc synergistically suppressed transcription-controlling genes and promoted transcription of genes involved in negative regulation of cell proliferation. RNA seq analysis also demonstrated the rewiring of glycolysis and TCA cycle by GM-CSF and CD137L co-signaling in BMDMs. Finally, we showed that absence of CD137L signaling had uncontrollable chronic renal inflammation in the unilateral ureteral obstruction model. Taken together, our results suggest that CD137L signaling is critical in resolution of tissue inflammation. 



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