한빛사논문
- 조회913
Min-Gang Kim1, Donghwan Yun1,2, Chae Lin Kang1,2, Minki Hong1,2, Juhyeon Hwang1,2, Kyung Chul Moon3, Chang Wook Jeong4, Cheol Kwak4, Dong Ki Kim2, Kook-Hwan Oh2, Kwon Wook Joo2, Yon Su Kim1,2, Dong-Sup Lee1,2,* and Seung Seok Han2,*
1Department of Biomedical Sciences, 2Department of Internal Medicine, 3Department of Pathology, and 4Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
Authorship note: MGK and DY are co-first authors
*Address correspondence to: Seung Seok Han, Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehakro, Jongno-gu, Seoul 03080, Korea. Or to: Dong-Sup Lee, Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehakro, Jongno-gu, Seoul 03080, Korea.
Abstract
Severe glomerular injury ultimately leads to tubulointerstitial fibrosis that determines patient outcome, but the immunological molecules connecting these processes remain undetermined. The present study addressed whether V-domain Ig suppressor of T cell activation (VISTA), constitutively expressed in kidney macrophages, plays a protective role in tubulointerstitial fibrotic transformation after acute antibody-mediated glomerulonephritis. After acute glomerular injury using nephrotoxic serum, tubules in the VISTA-deficient (Vsir–/–) kidney suffered more damage than those in WT kidneys. When interstitial immune cells were examined, the contact frequency of macrophages with infiltrated T cells increased and the immunometabolic features of T cells changed to showing high oxidative phosphorylation and fatty acid metabolism and overproduction of IFN-γ. The Vsir–/– parenchymal tissue cells responded to this altered milieu of interstitial immune cells as more IL-9 was produced, which augmented tubulointerstitial fibrosis. Blocking antibodies against IFN-γ and IL-9 protected the above pathological process in VISTA-depleted conditions. In human samples with acute glomerular injury (e.g., antineutrophil cytoplasmic autoantibody vasculitis), high VISTA expression in tubulointerstitial immune cells was associated with low tubulointerstitial fibrosis and good prognosis. Therefore, VISTA is a sentinel protein expressed in kidney macrophages that prevents tubulointerstitial fibrosis via the IFN-γ/IL-9 axis after acute antibody-mediated glomerular injury.
논문정보
- Research article
- 2022년 01월 (BRIC 등록일 2022-01-25)
- 국내 연구진
- 의약학 > 면역의학
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