Kidney Int. 2020;97(5):980-994.
Kidney residency of VISTA-positive macrophages accelerates repair from ischemic injury.
제1저자 박준규 · 교신저자 한승석, 이동섭
소속 (8)
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
- Kidney Research Institute, Seoul National University, Seoul, Korea.
- Kidney Research Institute, Seoul National University, Seoul, Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
- Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Kidney Research Institute, Seoul National University, Seoul, Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Kidney Research Institute, Seoul National University, Seoul, Korea. Electronic address: dlee5522@snu.ac.kr.
- Kidney Research Institute, Seoul National University, Seoul, Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. Electronic address: hansway80@gmail.com.
Abstract
Tissue-resident macrophages have unique tissue-specific functions in maintaining homeostasis and resolving inflammation. However, the repair role and relevant molecules of kidney-resident macrophages after ischemic injury remain unresolved. To this end, mice without kidney-resident R1 macrophages but containing infiltrating monocyte-derived R2 macrophages were generated using differential cellular kinetics following clodronate liposome treatment. When ischemia-reperfusion injury was induced in these mice, late phase repair was reduced. Transcriptomic and flow cytometric analyses identified that V-domain Ig suppressor of T cell activation (VISTA), an inhibitory immune checkpoint molecule, was constitutively expressed in kidney-resident R1 macrophages, but not in other tissue-resident macrophages. Here, VISTA functioned as a scavenger of apoptotic cells and served as a checkpoint to control kidney-infiltrating T cells upon T cell receptor-mediated stimulation. Together these functions improved the repair process after ischemia-reperfusion injury. CD14+ CD33+ mononuclear phagocytes of human kidney also expressed VISTA, which has similar functions to the mouse counterpart. Thus, VISTA is upregulated in kidney macrophages in a tissue-dependent manner and plays a repair role during ischemic injury.
Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Keywords
VISTAinflammationkidneyphagocytosisresident macrophage
그 밖의 정보
- 출판 형태
- Journal Article, Research Support, Non-U.S. Gov't
- 저널
- Kidney international · eISSN 1523-1755
- 전자 출판
- 2019-12-17
- MeSH
- Animals · Internship and Residency* · Ischemia · Kidney · Macrophages · Mice · Reperfusion Injury*