Kidney residency of VISTA-positive macrophages accelerates repair from ischemic injury

Jun-Gyu Park; Cho-Rong Lee; Min-Gang Kim; Gwanghun Kim; Hyun Mu Shin; Yun-Hui Jeon; Seung Hee Yang; Dong Ki Kim; Kwon Wook Joo; Eun Young Choi; Hang-Rae Kim; Cheol Kwak; Yon Su Kim; Murim Choi; Dong-Sup Lee; Seung Seok Han

doi:10.1016/j.kint.2019.11.025

Kidney residency of VISTA-positive macrophages accelerates repair from ischemic injury

Kidney Int. 2020 May;97(5):980-994. doi: 10.1016/j.kint.2019.11.025. Epub 2019 Dec 17.

Authors

Affiliations

¹ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
² Kidney Research Institute, Seoul National University, Seoul, Korea.
³ Kidney Research Institute, Seoul National University, Seoul, Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
⁴ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
⁵ Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
⁶ 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.
⁷ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Kidney Research Institute, Seoul National University, Seoul, Korea. Electronic address: [email protected].
⁸ Kidney Research Institute, Seoul National University, Seoul, Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. Electronic address: [email protected].

PMID: 32143848
DOI: 10.1016/j.kint.2019.11.025

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.

Keywords: VISTA; inflammation; kidney; phagocytosis; resident macrophage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Internship and Residency*
Ischemia
Kidney
Macrophages
Mice
Reperfusion Injury*