ArticleTransplantation2012
A20-mediated modulation of inflammatory and immune responses in aortic allografts and development of transplant arteriosclerosis.
Article in Transplantation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Advancements in Omics and Breakthrough Gene Therapies: A Glimpse into the Future of Peripheral Artery Disease.Annals of vascular surgery · 2024Review
- A20 in Kidney Transplantation and Autoimmunity.International journal of molecular sciences · 2024Review
- TNFAIP3 alleviates pain in lumbar disc herniation rats by inhibiting the NF-κB pathway.Annals of translational medicine · 2022Article
- A20/TNFAIP3 Increases ENOS Expression in an ERK5/KLF2-Dependent Manner to Support Endothelial Cell Health in the Face of Inflammation.Frontiers in cardiovascular medicine · 2021Article
- RAGE impairs murine diabetic atherosclerosis regression and implicates IRF7 in macrophage inflammation and cholesterol metabolism.JCI insight · 2020Article
- Article
- Abnormally expressed miR-23b in Chinese Mongolian at high cardiovascular risk may contribute to monocyte/macrophage inflammatory reaction in atherosclerosis.Bioscience reports · 2018Article
- TNFAIP3 F127C Coding Variation in Greek Primary Sjogren's Syndrome Patients.Journal of immunology research · 2018Article
- Constitutive expression of the anti-apoptotic Bcl-2 family member A1 in murine endothelial cells leads to transplant tolerance.Clinical and experimental immunology · 2017Article
- A20 Haploinsufficiency Aggravates Transplant Arteriosclerosis in Mouse Vascular Allografts: Implications for Clinical Transplantation.Transplantation · 2016Article
- Roles of A20 in autoimmune diseases.Immunologic research · 2016Review
- Zinc Prevents Abdominal Aortic Aneurysm Formation by Induction of A20-Mediated Suppression of NF-κB Pathway.PloS one · 2016Article
- A20 suppresses vascular inflammation by recruiting proinflammatory signaling molecules to intracellular aggresomes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- A20 regulates atherogenic interferon (IFN)-γ signaling in vascular cells by modulating basal IFNβ levels.The Journal of biological chemistry · 2014Article
- Treg functional stability and its responsiveness to the microenvironment.Immunological reviews · 2014Review
- Immune-mediated vascular injury and dysfunction in transplant arteriosclerosis.Frontiers in immunology · 2014Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTransplant arteriosclerosis (TA) is the pathognomonic feature of chronic rejection, the primary cause of allograft failure. We have shown that the NF-κB inhibitory protein A20 exerts vasculoprotective effects in endothelial and smooth muscle cells (SMC), and hence is a candidate to prevent TA. We sought direct proof for this hypothesis.
methodsFully mismatched, C57BL/6 (H2) into BALB/c (H2), aorta to carotid allografts were preperfused with saline, recombinant A20 adenovirus (rAd.A20) or rAd.β-galactosidase (β-gal), implanted, harvested 4 weeks after transplantation, and analyzed by histology, immunohistochemistry, and immunofluorescence staining. We measured indoleamine 2,3-dioxygenase, interleukin-6, and transforming growth factor-β mRNA and protein levels in nontransduced, and rAd.A20 or rAd.β-gal-transduced human SMC cultures after cytokine treatment.
resultsVascular overexpression of A20 significantly reduced TA lesions. This correlated with decreased graft inflammation and increased apoptosis of neointimal SMC. Paradoxically, T-cell infiltrates increased in A20-expressing allografts, including the immunoprivileged media, which related to A20 preventing indoleamine 2,3-dioxygenase upregulation in SMC. However, infiltrating T cells were predominantly T-regulatory cells (CD25+/Forkhead Box P3 [FoxP3+]). This agrees with A20 inhibiting interleukin-6 and promoting transforming growth factor-β production by medial SMC and in SMC cultures exposed to cytokines, which favors differentiation of regulatory over pathogenic T cells.
conclusionsIn summary, A20 prevents immune-mediated remodeling of vascular allografts, therefore reduces TA lesions by affecting apoptotic and inflammatory signals and modifying the local cytokine milieu to promote an immunoregulatory response within the vessel wall. This highlights a novel function for A20 in local immunosurveillance, which added to its vasculoprotective effects, supports its therapeutic promise in TA.
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