대한신장학회

논문분류	춘계학술대회 초록집
제목	VISTA-dependent role of resident macrophages in kidney homeostasis and inflammation
저자	Jungyu Park2, Min Ji Kim2, Yun-Hui Jeon2, Seung Hee Yang3, Dong Ki Kim1, Yon Su Kim1, Dong-Sup Lee2, Seung Seok Han1
출판정보	2018; 2018(1):
키워드	Homeostasis \| Inflammation \| Macrophage \| Resident \| VISTA
초록	Objectives: V-domain Ig suppressor of T cell activation (VISTA), expressed primarily on antigen-presenting cells, has been known to participate in the progression of cancer through an immune checkpoint. Nevertheless, both the expression pattern and role of VISTA within kidney environment remain unresolved. Methods: . Results: Mouse kidney myeloid cells were categorized based on the expression of CD11b and F4/80 as follows: kidney resident macrophage (rMΦ) (CD11bint F4/80high), bone marrow-derived MΦ (CD11bhigh F4/80int Ly6G-), and neutrophils (CD11bhigh F4/80low Ly6G+). Kidney rMΦ expressed CD11c, MHC II, CD86, and CX3CR1 together, but did not express CD80, Ly6C, Ly6G, CD115, or CCR2. When rMΦ was predominantly depleted by clodronate liposome, the degree of ischemic renal injury (IRI) was reduced. Intriguingly, all rMΦs expressed VISTA in normal kidneys, but not other immune checkpoints, including CD273, CD274, or galectin-9. The VISTA expression of rMΦ differed between organs: high expression was found only in the kidneys and peritoneum. The high VISTA expression in kidney rMΦ was retained throughout the life and even after IRI. In the VISTA overexpression experiments, using bone marrow-derived MΦ and dendritic cells, VISTA increased the efferocytotic efficacy against apoptotic cells and conferred negative signals to antigen-presented T cells. It has been known that the kidney rMΦ is scarcely replaced by the bone marrow-derived cells in adulthood. When this issue was addressed in the post-inflammatory environment using parabiosis mouse model (parabionts were harvested after 1 month of unilateral IRI), the proportion of rMΦ originated from paired parabionts was higher in injured kidneys than in counterpart non-injured kidneys, and their VISTA expressions were high irrespective of origins. Conclusions: These data indicate that VISTA, distinctively shown in kidney rMΦ and highly maintained within kidney environment, functions via phagocytosis and crosstalk with lymphocytes in both homeostatic and inflammatory status. Figure 1. Characterization of kidney resident macrophages
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