Costimulatory molecule VSIG4 exclusively expressed on macrophages alleviates renal tubulointerstitial injury in VSIG4 KO mice

Li, Yan; Wang, Yiqin; Wang, Daihong; Hou, Wugang; Zhang, Ying; Li, Ming; Li, Furong; Mu, Jian; Du, Xiang; Pang, Fang; Yuan, Fang

doi:10.1007/s40620-013-0022-3

Cited by 13 publications

(7 citation statements)

References 21 publications

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“…CRIg expression has been associated with decreased T cell and B cell responses (5,44). The importance of CRIg in protecting against autoimmune inflammation has been demonstrated in experimental models of inflammatory arthritis (45), renal tubulointestitial injury (46), lupus nephritis (47), immune-mediated liver injury (48), type 1 diabetes (7,30), and inflammatory bowel disease (49). In addition, the levels of CRIg expression in macrophages has been associated with disease severity in rheumatoid arthritis (31,50) and patients with cirrhosis and ascites (51).…”

Section: Discussionmentioning

confidence: 99%

Human Dendritic Cells Express the Complement Receptor Immunoglobulin Which Regulates T Cell Responses

et al. 2019

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The B7 family-related protein V-set and Ig containing 4 (VSIG4), also known as Z39Ig and Complement Immunoglobulin Receptor (CRIg), is the most recent of the complement receptors to be identified, with substantially distinct properties from the classical complement receptors. The receptor displays both phagocytosis-promoting and anti-inflammatory properties. The receptor has been reported to be exclusively expressed in macrophages. We now present evidence, that CRIg is also expressed in human monocyte-derived dendritic cells (MDDC), including on the cell surface, implicating its role in adaptive immunity. Three CRIg transcripts were detected and by Western blotting analysis both the known Long (L) and Short (S) forms were prominent but we also identified another form running between these two. Cytokines regulated the expression of CRIg on dendritic cells, leading to its up-or down regulation. Furthermore, the steroid dexamethasone markedly upregulated CRIg expression, and in co-culture experiments, the dexamethasone conditioned dendritic cells caused significant inhibition of the phytohemagglutinin-induced and alloantigen-induced T cell proliferation responses. In the alloantigen-induced response the production of IFNγ, TNF-α, IL-13, IL-4, and TGF-β1, were also significantly reduced in cultures with dexamethasone-treated DCs. Under these conditions dexamethasone conditioned DCs did not increase the percentage of regulatory T cells (Treg). Interestingly, this suppression could be overcome by the addition of an anti-CRIg monoclonal antibody to the cultures. Thus, CRIg expression may be a control point in dendritic cell function through which drugs and inflammatory mediators may exert their tolerogenic-or immunogenic-promoting effects on dendritic cells.

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Section: Discussionmentioning

confidence: 99%

Human Dendritic Cells Express the Complement Receptor Immunoglobulin Which Regulates T Cell Responses

et al. 2019

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“…It can be inferred that VSIG4 is an important gene that inhibits the activation of M1 pro-inflammatory macrophages. Moreover, CD3/4/8 and interferon-γ (IFN-γ) levels are extremely lower in unilateral ureteral obstruction (UUO)-induced VSIG +/+ mice than those in the (UUO)induced VSIG -/mice, indicating that macrophageexpressed VSIG-4 relieves renal tubulointerstitial injury by inhibiting T cell infiltration and the expression of inflammatory factors (32). Inflammation, as a major driver of recruitment of immune cells (including macrophages), is closely associated with the development of the disease.…”

Section: Discussionmentioning

confidence: 99%

VSIG4 overexpression alleviates acute kidney injury of mice via inhibition of M1-macrophages activation

Liu

et al. 2022

Ann Transl Med

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Background: The infiltration and activation of M1-macrophages can promote renal tubular interstitial damage. The study aimed to investigate the effect of V-set and immunoglobulin domain containing 4 (VSIG4) on M1-macrophages activation and acute kidney injury (AKI) mice. Methods:The M1-macrophage markers cluster of differentiation 86 (CD86) and inducible nitric oxide synthase (iNOS) were detected via flow cytometry. Cell viability and expression of inflammatory factors were analyzed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), as well as quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) assays. Moreover, HK-2 cells stimulated with lipopolysaccharide (LPS) and RAW264.7 cells overexpressing VSIG4 were co-cultured to analyze the effect of VSIG4 suppressing M1macrophage activation on HK-2 cells via detecting cell proliferation and apoptosis levels. Furthermore, the pathological changes and iNOS expression of kidney tissue in VSIG4 knockout mice with renal ischemiareperfusion injury (IRI) were detected by hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining.Results: Overexpression of VSIG4 partially reversed the phenomenon of M1-macrophageactivation caused by LPS-upregulated CD86 and iNOS expression, reduced cell viability, and induced the expression levels of interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in RAW264.7. In addition, RAW264.7 cells overexpressing VSIG4 could also alleviate the low proliferation and high apoptotic level of HK-2 cells stimulated with LPS. After VSIG4 knockout, the kidney tissue of AKI mice showed obvious lesions and iNOS expression, indicating that VSIG4 knockout promoted the infiltration of M1-macrophages in the damaged kidney tissue and accelerated kidney tissue lesions.Conclusions: Overexpression of VSIG4 might alleviate the lesions of kidney tissue in AKI mice via inhibition of the secretion of inflammatory factors in M1-macrophages.

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“…CD46 shares activities with CR1 in that it binds C3b and C4b, and protects host cells from complement mediated damage. Its intriguing that VSIG4, which protects the vascular system from alternative pathway activation by clearing hydrolyzed C3 from the blood and preventing its association with C5 (10), is also a negative regulator of T cell function (11,92,121,122). The high expression of VSIG4 in the liver and peritoneal cavity may help establish a level of immune privilege in these sites (123), although the role of VSIG4 has not been investigated.…”

Section: Complement In T Cell Activationmentioning

confidence: 99%

Complement Receptors in Myeloid Cell Adhesion and Phagocytosis

Dustin

2017

Myeloid Cells in Health and Disease

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Myeloid cells make extensive use of the complement system in the context of recruitment, phagocytosis and other effector functions. There are several types of complement receptors on myeloid cells including G-proteins coupled receptors for localizing the source of complement activation, and three sets of type I transmembrane proteins that link complement to phagocytosiscomplement receptor 1, a single chain type I membrane protein with tandem complement regulatory repeats, complement receptors 3 and 4, which are integrin family receptors comprised of heterodimers of type I transmembrane subunits, and VSIG4, member of the Ig-superfamily. This review will focus the role of the different classes of complement receptors and how their activities are integrated in the setting of immune tolerance and inflammatory responses.

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Costimulatory molecule VSIG4 exclusively expressed on macrophages alleviates renal tubulointerstitial injury in VSIG4 KO mice

Abstract: The macrophage-expressed VSIG4 may act to alleviate renal tubulointerstitial injury via inhibition of T cell infiltration and secretion of inflammation related factors.

Cited by 13 publications

References 21 publications

Human Dendritic Cells Express the Complement Receptor Immunoglobulin Which Regulates T Cell Responses

Human Dendritic Cells Express the Complement Receptor Immunoglobulin Which Regulates T Cell Responses

VSIG4 overexpression alleviates acute kidney injury of mice via inhibition of M1-macrophages activation

Complement Receptors in Myeloid Cell Adhesion and Phagocytosis

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