Kidney International, 2020.97(5), 980-994, DOI: https://doi.org/10.1016/j.kint.2019.11.025

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

Park JG, Lee CR;Kim MG;Kim G;Shin H;Jeon YH;Yang S;Kim D;Joo K;Choi E;Kim HR;Kwak C;Kim Y;Choi M;Lee DS;Han S

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 kidneyresident 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.
Tranomic 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. CD14D CD33D 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.

• DOI: https://doi.org/10.1016/j.kint.2019.11.025
• ISBN or ISSN: 0085-2538

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.