Abstract
Inflammation is the result of acute and chronic stresses, caused by emotional or physical
trauma, or nutritional or environmental pollutants, and brings serious harm to human
life and health. As an important cellular component of the innate immune barrier,
the macrophage plays a key role in maintaining tissue homeostasis and promoting tissue
repair by controlling infection and resolving inflammation. Several studies suggest
that V Set and Ig domain-containing 4 is specifically expressed in tissue macrophages
and is associated with a variety of inflammatory diseases. In this paper, we mainly
summarize the recent research on V Set and Ig domain-containing 4 structures, functions,
function and roles in acute and chronic inflammatory diseases, and provide a novel
therapeutic avenue for the treatment of inflammatory diseases, including nervous system,
urinary, respiratory and metabolic diseases.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to CytotherapyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- VSIG4, a B7 family-related protein, is a negative regulator of T cell activation.J Clin Invest. 2006; 116: 2817-2826
- Cloning of Z39Ig, a novel gene with immunoglobulin-like domains located on human chromosome X.Biochimica et biophysica acta. 2000; 1492: 522-525
- CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens.Cell. 2006; 124: 915-927
- Macrophage complement receptors and pathogen clearance.Cellular microbiology. 2007; 9: 2095-2102
- Z39Ig is co-expressed with activated macrophage genes.Biochim Biophys Acta. 2002; 1574: 387-390
- IL-12, IL-23 and IL-17 in IBD: immunobiology and therapeutic targeting.Nature reviews Gastroenterology & hepatology. 2019; 16: 185-196
- The IL-23/IL-17 pathway in human chronic inflammatory diseases-new insight from genetics and targeted therapies.Genes and immunity. 2019; 20: 415-425
- Z39Ig is expressed on macrophages and may mediate inflammatory reactions in arthritis and atherosclerosis.J Leukoc Biol. 2006; 80: 922-928
- Highly accurate protein structure prediction with AlphaFold.Nature. 2021; 596: 583-589
- AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models.Nucleic Acids Research. 2021; 50: D439-DD44
- Post-translational modification: nature's escape from genetic imprisonment and the basis for dynamic information encoding.Wiley interdisciplinary reviews Systems biology and medicine. 2012; 4: 565-583
Munawara U, Perveen K, Small A, Putty T, Quach A, Gorgani N, et al. Human dendritic cells express the complement receptor immunoglobulin which regulates T cell responses. 2019;10:2892.
- Identification of the genes differentially expressed in human dendritic cell subsets by cDNA subtraction and microarray analysis.Blood. 2002; 100: 1742-1754
Gorgani N, Thathaisong U, Mukaro V, Poungpair O, Tirimacco A, Hii C, et al. Regulation of CRIg expression and phagocytosis in human macrophages by arachidonate, dexamethasone, and cytokines. 2011;179(3):1310-8.
- Protein kinase cα regulates the expression of complement receptor Ig in human monocyte-derived macrophages.J Immunol. 2015; 194: 2855-2861
Liu G, Fu Y, Yosri M, Chen Y, Sun P, Xu J, et al. CRIg plays an essential role in intravascular clearance of bloodborne parasites by interacting with complement. 2019;116(48):24214-20.
- CRIg mediates early Kupffer cell responses to adenovirus.J Leukoc Biol. 2013; 93: 301-306
- Dual-track clearance of circulating bacteria balances rapid restoration of blood sterility with induction of adaptive immunity.Cell Host Microbe. 2016; 20: 36-48
- Extracellular stimulation of VSIG4/complement receptor Ig suppresses intracellular bacterial infection by inducing autophagy.Autophagy. 2016; 12: 1647-1659
- Complement receptor of the Ig superfamily enhances complement-mediated phagocytosis in a subpopulation of tissue resident macrophages.J Immunol. 2008; 181: 7902-7908
- CRIg signals induce anti-intracellular bacterial phagosome activity in a chloride intracellular channel 3-dependent manner.Eur J Immunol. 2013; 43: 667-678
- Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion.The Journal of cell biology. 2016; 212: 181-198
- Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy.Cell. 2013; 152: 290-303
- MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages.The Journal of biological chemistry. 2008; 283: 33175-33182
- Outside in: Roles of complement in autophagy.British journal of pharmacology. 2021; 178: 2786-2801
- Structure of C3b in complex with CRIg gives insights into regulation of complement activation.Nature. 2006; 444: 217-220
Jiang H, Wang Z, Serra D, Frank M, Amalfitano AJMT. Recombinant adenovirus vectors activate the alternative complement pathway, leading to the binding of human complement protein C3 independent of anti-Ad antibodies. 2004; 10(6): 1140-2.
Manickan E, Smith JS, Tian J, Eggerman TL, Lozier JN, Muller J, et al. Rapid Kupffer cell death after intravenous injection of adenovirus vectors. 2006; 13(1): 108-17.
Di Paolo NC, Doronin K, Baldwin LK, Papayannopoulou T, Shayakhmetov DMJCR. The transcription factor IRF3 triggers “defensive suicide” necrosis in response to viral and bacterial pathogens. 2013;3(6):1840-6.
- MMP9 inhibition increases autophagic flux in chronic heart failure.Am J Physiol Heart Circ Physiol. 2020; 319 (H1414-h37)
- Protective role of V-set and immunoglobulin domain-containing 4 expressed on Kupffer cells during immune-mediated liver injury by inducing tolerance of liver T- and natural killer T-cells.Hepatology. 2012; 56: 1838-1848
- p27kip1 functions as an anergy factor inhibiting interleukin 2 transcription and clonal expansion of alloreactive human and mouse helper T lymphocytes.Nature medicine. 2000; 6: 290-297
- Opposing roles for the cyclin-dependent kinase inhibitor p27kip1 in the control of CD4+ T cell proliferation and effector function.J Immunol. 2005; 174: 3359-3368
- Induction of T cells suppression by dendritic cells transfected with VSIG4 recombinant adenovirus.Immunol Lett. 2010; 128: 46-50
- VSIG4 expression on macrophages facilitates lung cancer development.Lab Invest. 2014; 94: 706-715
- The new complement inhibitor CRIg/FH ameliorates lupus nephritis in lupus-prone MRL/lpr mice.BMC Nephrol. 2019; 20: 424
- Complement receptor of the immunoglobulin superfamily reduces murine lupus nephritis and cutaneous disease.Clin Immunol. 2015; 160: 286-291
- The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology to in vivo imaging.Neural Regen Res. 2019; 14: 373-386
- VSIG4 mediates transcriptional inhibition of Nlrp3 and Il-1β in macrophages.Sci Adv. 2019; 5: eaau7426
- VSIG4 attenuates NLRP3 and ameliorates neuroinflammation via JAK2-STAT3-A20 pathway after intracerebral hemorrhage in mice.Neurotox Res. 2022; 40: 78-88
- Novel targets, treatments, and advanced models for intracerebral haemorrhage.EBioMedicine. 2022; 76103880
- VSIG4 alleviates intracerebral hemorrhage induced brain injury by suppressing TLR4-regulated inflammatory response.Brain Res Bull. 2021; 176: 67-75
- Microglial V-set and immunoglobulin domain-containing 4 protects against ischemic stroke in mice by suppressing TLR4-regulated inflammatory response.Biochem Biophys Res Commun. 2020; 522: 560-567
- VSIG4 is highly expressed and correlated with poor prognosis of high-grade glioma patients.American journal of translational research. 2015; 7: 1172-1180
- A role of macrophage complement receptor CRIg in immune clearance and inflammation.Mol Immunol. 2008; 45: 4041-4047
- Advances in targeting cell surface signalling molecules for immune modulation.Nature reviews Drug discovery. 2013; 12: 130-146
- Let-7g-5p inhibits epithelial-mesenchymal transition consistent with reduction of glioma stem cell phenotypes by targeting VSIG4 in glioblastoma.Oncol Rep. 2016; 36: 2967-2975
- Inflammatory bowel disease 2017: innovations and changing paradigms.Gastroenterology. 2017; 152: 309-312
- Pterostilbene 4′-β-glucoside protects against DSS-induced colitis via induction of tristetraprolin.Oxidative medicine and cellular longevity. 2017; 20179427583
- Resveratrol attenuates inflammatory bowel disease in mice by regulating SUMO1.Biological & pharmaceutical bulletin. 2020; 43: 450-457
- Cross-talk between CD38 and TTP is essential for resolution of inflammation during microbial sepsis.Cell reports. 2020; 30 (1063-76.e5)
- CD1d1 intrinsic signaling in macrophages controls NLRP3 inflammasome expression during inflammation.Sci Adv. 2020; 6
- Phenotypic and functional profiles of CRIg (Z39Ig)-expressing macrophages in the large intestine.Innate Immun. 2012; 18: 258-267
- Host attachment and fluid shear are integrated into a mechanical signal regulating virulence in Escherichia coli O157:H7.Proc Natl Acad Sci U S A. 2015; 112: 5503-5508
- B7 Family molecule VSIG4 regulates intestinal anti-enterohemorrhagic Escherichia coli immunity by altering gut flora diversity.Microorganisms. 2021; 9
- Revised estimates for the number of human and bacteria cells in the body.PLoS Biol. 2016; 14e1002533
- VSIG4 inhibits proinflammatory macrophage activation by reprogramming mitochondrial pyruvate metabolism.Nat Commun. 2017; 8: 1322
- Low expression of VSIG4 is associated with poor prognosis in hepatocellular carcinoma patients with hepatitis B infection.Cancer Manag Res. 2018; 10: 3697-3705
- Expression of Vsig4 attenuates macrophage-mediated hepatic inflammation and fibrosis in high fat diet (HFD)-induced mice.Biochem Biophys Res Commun. 2019; 516: 858-865
- Autoimmune hepatitis.Nat Rev Dis Primers. 2018; 4: 18017
- Incidence, prevalence and mortality of autoimmune hepatitis in England 1997-2015. A population-based cohort study.Liver Int. 2020; 40: 1634-1644
- Regulatory T cells in autoimmune hepatitis: unveiling their roles in mouse models and patients.Front Immunol. 2020; 11575572
- A global scientific strategy to cure hepatitis B.Lancet Gastroenterol Hepatol. 2019; 4: 545-558
- Histopathological evaluation of long-term tenofovir disoproxil fumarate treatment in patients with hepatitis be antigen-negative chronic hepatitis B.World J Gastrointest Pharmacol Ther. 2021; 12: 32-39
- Down-regulation of Z39Ig on macrophages by IFN-gamma in patients with chronic HBV infection.Clin Immunol. 2010; 136: 282-291
- The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases.Hepatology. 2018; 67: 328-357
- Epidemiology and effects of bacterial infections in patients with cirrhosis worldwide.Gastroenterology. 2019; 156 (1368-80 e10)
- PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis.J Hepatol. 2021; 74: 1097-1108
- Immunomodulatory receptor VSIG4 is released during spontaneous bacterial peritonitis and predicts short-term mortality.JHEP Rep. 2022; 4100391
- Insulin gene therapy for type 1 diabetes mellitus.Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2015; (13 Suppl 1): 37-45
- Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies.Diabetologia. 2016; 59: 237-243
- CD8+ T cells in autoimmunity.Current opinion in immunology. 2005; 17: 624-631
- Genetics, pathogenesis and clinical interventions in type 1 diabetes.Nature. 2010; 464: 1293-1300
- CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells.Elife. 2017; 6
- Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging.Nat Immunol. 2012; 13: 361-368
- An integrated view of immunometabolism.Cell. 2018; 172: 22-40
- The integrative biology of type 2 diabetes.Nature. 2019; 576: 51-60
- The origins and drivers of insulin resistance.Cell. 2013; 152: 673-684
- Inflammation, metaflammation and immunometabolic disorders.Nature. 2017; 542: 177-185
- Inflammatory mechanisms linking obesity and metabolic disease.J Clin Invest. 2017; 127: 1-4
- Accumulation of microbial DNAs promotes to islet inflammation and beta cell abnormalities in obesity in mice.Nat Commun. 2022; 13: 565
- CRIg(+) macrophages prevent gut microbial DNA-containing extracellular vesicle-induced tissue inflammation and insulin resistance.Gastroenterology. 2021; 160: 863-874
- VSIG4 induces epithelial-mesenchymal transition of renal tubular cells under high-glucose conditions.Life (Basel). 2020; 10
- Identification of key genes and pathways in diabetic nephropathy by bioinformatics analysis.J Diabetes Investig. 2019; 10: 972-984
- Design and application of single-cell RNA sequencing to study kidney immune cells in lupus nephritis.Nat Rev Nephrol. 2020; 16: 238-250
- The molecular phenotype of endocapillary proliferation: novel therapeutic targets for IgA nephropathy.PLoS One. 2014; 9e103413
- Regulation of DNA damage signaling and cell death responses by Epstein-Barr virus latent membrane protein 1 (LMP1) and LMP2A in nasopharyngeal carcinoma cells.Journal of virology. 2015; 89: 7612-7624
- Epstein-Barr virus-encoded latent membrane protein 1 induces epithelial to mesenchymal transition by inducing V-set Ig domain containing 4 (VSIG4) expression via NF-kB in renal tubular epithelial HK-2 cells.Biochem Biophys Res Commun. 2017; 492: 316-322
- Costimulatory molecule VSIG4 exclusively expressed on macrophages alleviates renal tubulointerstitial injury in VSIG4 KO mice.Journal of Nephrology. 2014; 27: 29-36
- SARS-CoV-2 detection in different respiratory sites: A systematic review and meta-analysis.EBioMedicine. 2020; 59102903
- Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients.Cell Mol Immunol. 2020; 17: 541-543
- Goals of COPD treatment: Focus on symptoms and exacerbations.Respir Med. 2020; 166105938
Organization WH. The top 10 causes of death. 2018 (accessed 7 November 2019)
- Leading causes for 2017.Natl Vital Stat Rep. 2019;
- Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet. 2018; 392: 1789-1858
- Defective macrophage phagocytosis of bacteria in COPD.The European respiratory journal. 2010; 35: 1039-1047
- Proteome profiling of lung tissues in chronic obstructive pulmonary disease (COPD): platelet and macrophage dysfunction contribute to the pathogenesis of COPD.Int J Chron Obstruct Pulmon Dis. 2020; 15: 973-980
- Phosphodiesterase isoforms and cAMP compartments in the development of new therapies for obstructive pulmonary diseases.Curr Opin Pharmacol. 2020; 51: 34-42
- Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy.Lancet Respir Med. 2020; 8: 807-815
- Healing after COVID-19: are survivors at risk for pulmonary fibrosis?.Am J Physiol Lung Cell Mol Physiol. 2021; 320 (L257-l65)
- Aging and lung disease.Annu Rev Physiol. 2020; 82: 433-459
- Cellular senescence mediates fibrotic pulmonary disease.Nat Commun. 2017; 8: 14532
- SnapShot: Cellular senescence pathways.Cell. 2017; 170 (816-.e1)
- Cellular senescence as a mechanism and target in chronic lung diseases.Am J Respir Crit Care Med. 2019; 200: 556-564
- Alveolar epithelial type II cells as drivers of lung fibrosis in idiopathic pulmonary fibrosis.Int J Mol Sci. 2020; 21
- Senescence of alveolar type 2 cells drives progressive pulmonary fibrosis.Am J Respir Crit Care Med. 2021; 203: 707-717
- Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis.Respir Res. 2018; 19: 175
- Gasotransmitter CO attenuates bleomycin-induced fibroblast senescence via induction of stress granule formation.Oxid Med Cell Longev. 2021; 20219926284
- TRIM72 promotes alveolar epithelial cell membrane repair and ameliorates lung fibrosis.Respir Res. 2020; 21: 132
- Inhibition of macrophage complement receptor CRIg by TRIM72 polarizes innate immunity of the lung.Am J Respir Cell Mol Biol. 2018; 58: 756-766
- The incidence of cancer in patients with idiopathic pulmonary fibrosis and sarcoidosis in the UK.Respir Med. 2007; 101: 2534-2540
- Morphologic and molecular study of lung cancers associated with idiopathic pulmonary fibrosis and other pulmonary fibroses.Respir Res. 2017; 18: 120
- Paired genetic analysis by next-generation sequencing of lung cancer and associated idiopathic pulmonary fibrosis.Cancer Sci. 2020; 111: 2482-2487
- A novel inhibitor of the alternative pathway of complement reverses inflammation and bone destruction in experimental arthritis.J Exp Med. 2007; 204: 1319-1325
- Inhibition of the alternative pathway of complement activation reduces inflammation in experimental autoimmune uveoretinitis.Eur J Immunol. 2010; 40: 2870-2881
- Immune checkpoint protein VSIG4 as a biomarker of aging in murine adipose tissue.Aging Cell. 2020; 19: e13219
- The significance of VSIG4 expression in ovarian cancer.Int J Gynecol Cancer. 2017; 27: 872-878
- Gene expression differences in adipose tissue associated with breast tumorigenesis.Adipocyte. 2014; 3: 107-114
- The immune checkpoint molecule V-set Ig domain-containing 4 is an independent prognostic factor for multiple myeloma.Oncotarget. 2017; 8: 58122-58132
- VSIG4(+) peritoneal macrophages induce apoptosis of double-positive thymocyte via the secretion of TNF-alpha in a CLP-induced sepsis model resulting in thymic atrophy.Cell Death Dis. 2021; 12: 526
- Endogenous VSIG4 negatively regulates the helper T cell-mediated antibody response.Immunol Lett. 2015; 165: 78-83
Article info
Publication history
Published online: January 13, 2023
Accepted:
December 14,
2022
Received:
October 18,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
