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

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

doi:10.1016/j.kint.2019.11.025

Cited by 21 publications

(23 citation statements)

References 38 publications

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“…The proportions of macrophages were 45.4% ± 4.0% and 39.2% ± 4.0% in 8-week- and 1-year-old mice, respectively. When macrophages were categorized into kidney-resident (rMac: CD11b low F4/80 high ) and kidney-infiltrating (iMac: CD11b high F4/80 low ) subsets 20 , 21 , more than 90% were rMac (Fig. 5 b).…”

Section: Resultsmentioning

confidence: 99%

Immune cell composition in normal human kidneys

Park

Kim

et al. 2020

Sci Rep

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An understanding of immunological mechanisms in kidney diseases has advanced using mouse kidneys. However, the profiling of immune cell subsets in human kidneys remains undetermined, particularly compared with mouse kidneys. Normal human kidneys were obtained from radically nephrectomised patients with urogenital malignancy (n = 15). Subsequently, human kidney immune cell subsets were analysed using multicolor flow cytometry and compared with subsets from C57BL/6 or BALB/c mice under specific pathogen-free conditions. Twenty kidney sections from healthy kidney donors or subjects without specific renal lesions were additionally analysed by immunohistochemistry. In human kidneys, 47% ± 12% (maximum 63%) of immune cells were CD3+ T cells. Kidney CD4+ and CD8+ T cells comprised 44% and 56% of total T cells. Of these, 47% ± 15% of T cells displayed an effector memory phenotype (CCR7− CD45RA− CD69−), and 48% ± 19% were kidney-resident cells (CCR7− CD45RA− CD69+). However, the proportions of human CD14+ and CD16+ myeloid cells were approximately 10% of total immune cells. A predominance of CD3+ T cells and a low proportion of CD14+ or CD68+ myeloid cells were also identified in healthy human kidney sections. In mouse kidneys, kidney-resident macrophages (CD11blow F4/80high) were the most predominant subset (up to 50%) but the proportion of CD3+ T cells was less than 20%. These results will be of use in studies in which mouse results are translated into human cases under homeostatic conditions or with disease.

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Section: Resultsmentioning

confidence: 99%

Immune cell composition in normal human kidneys

Park

Kim

et al. 2020

Sci Rep

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“…The role of PSGL-1 as an immune checkpoint has been clarified in conditions such as wound healing or in tumors, where the pH can be 5.85-6.5 [25][26][27]; it is reasonable to speculate that human PSGL-1 is a binding partner of human VISTA at the low pH that is commonly found in tumors (Figure 2D-F) [3]. An acidic pH-selective VISTA mAb that blocks the PSGL-1/VISTA interaction increases IFN-γ production, NF-κB phosphorylation, and cell proliferation of human CD4 + T cells cocultured with VISTA-expressing cells in vitro [3].…”

Section: Psgl-1 In Malignancymentioning

confidence: 99%

VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy

Yuan

Tatineni

Mahoney

et al. 2021

Trends in Immunology

125

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V-domain Ig suppressor of T cell activation (VISTA) is a B7 family member that maintains T cell and myeloid quiescence and is a promising target for combination cancer immunotherapy. During inflammatory challenges, VISTA activity reprograms macrophages towards reduced production of proinflammatory cytokines and increased production of interleukin (IL)-10 and other anti-inflammatory mediators. The interaction of VISTA with its ligands is regulated by pH, and the acidic pH ~6.0 in the tumor microenvironment (TME) facilitates VISTA binding to P-selectin glycoprotein ligand 1 (PSGL-1). Targeting intratumoral pH might be a way to reduce the immunoinhibitory activity of the VISTA pathway and enhance antitumor immune responses. We review differences among VISTA therapeutics under development as candidate immunotherapies, focusing on VISTA binding partners and the unique structural features of this interaction.

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“…( 45 ) found renal repair after ischemic AKI in mice lacking kidney resident CD45 + Ly6G − F4/80 high CD11b int macrophages but containing infiltrating CD45 + Ly6G − F4/80 int CD11b high macrophages is delayed compared to the wide type mice. V-domain Ig suppressor of T cell activation (VISTA), an inhibitory immune checkpoint molecule, is mainly expressed by CD45 + Ly6G − F4/80 high CD11b int kidney resident macrophages and has the biomarker potential in distinguishing the renal macrophages ( 45 ). CX3CR1 mediated phagocytes by kidney resident macrophages initiate within the first hours during the innate host defense against Candidiasis , confirmed by CX3CR1-M280 associated susceptibility to systemic candidiasis in humans ( 46 ).…”

Section: Kidney Resident Macrophage Origin and Specificitymentioning

confidence: 99%

Macrophage Heterogeneity in Kidney Injury and Fibrosis

et al. 2021

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Kidney macrophages are central in kidney disease pathogenesis and have therapeutic potential in preventing tissue injury and fibrosis. Recent studies highlighted that kidney macrophages are notably heterogeneous immune cells that fulfill opposing functions such as clearing deposited pathogens, maintaining immune tolerance, initiating and regulating inflammatory responses, promoting kidney fibrosis, and degrading the extracellular matrix. Macrophage origins can partially explain macrophage heterogeneity in the kidneys. Circulating Ly6C+ monocytes are recruited to inflammatory sites by chemokines, while self-renewed kidney resident macrophages contribute to kidney repair and fibrosis. The proliferation of resident macrophages or infiltrating monocytes provides an alternative explanation of macrophage accumulation after kidney injury. In addition, dynamic Ly6C expression on infiltrating monocytes accompanies functional changes in handling kidney inflammation and fibrosis. Mechanisms underlying kidney macrophage heterogeneity, either by recruiting monocyte subpopulations, regulating macrophage polarization, or impacting distinctive macrophage functions, may help develop macrophage-targeted therapies for kidney diseases.

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

Cited by 21 publications

References 38 publications

Immune cell composition in normal human kidneys

Immune cell composition in normal human kidneys

VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy

Macrophage Heterogeneity in Kidney Injury and Fibrosis

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