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.

中文翻译：

---

肾脏驻留VISTA阳性巨噬细胞可加速缺血性损伤的修复。

驻留在组织中的巨噬细胞在维持体内平衡和解决炎症方面具有独特的组织特异性功能。然而，缺血性损伤后肾脏驻留巨噬细胞的修复作用和相关分子仍未得到解决。为此，在氯膦酸盐脂质体处理后，利用差分细胞动力学产生了没有肾驻留R1巨噬细胞但含有浸润的单核细胞衍生的R2巨噬细胞的小鼠。当在这些小鼠中引起缺血-再灌注损伤时，后期修复减少。转录组学和流式细胞仪分析确定，T细胞活化的V域Ig抑制剂（VISTA）是一种抑制性免疫检查点分子，在肾脏驻留R1巨噬细胞中组成性表达，而在其他组织驻留巨噬细胞中不表达。这里，VISTA充当凋亡细胞的清除剂，并充当在T细胞受体介导的刺激下控制肾浸润T细胞的检查点。这些功能共同改善了缺血再灌注损伤后的修复过程。人肾脏的CD14 + CD33 +单核吞噬细胞也表达VISTA，其功能与小鼠相似。因此，VISTA以组织依赖性方式在肾巨噬细胞中上调，并在缺血性损伤中发挥修复作用。