Dendritic cell marker Clec4a4 deficiency limits atherosclerosis progression

Background and aims: Atherogenesis results from altered lipid metabolism and impaired immune response. Emerging evidence has suggested that dendritic cells (DCs) participate to atherosclerosis-related immune response, but their impact is scarcely characterized. Clec4a4 or DCIR2 (Dendritic cell immun...

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Main Authors: Rossella Bellini, Annalisa Moregola, Jasmine Nour, Yoann Rombouts, Olivier Neyrolles, Patrizia Uboldi, Fabrizia Bonacina, Giuseppe Danilo Norata
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:Atherosclerosis Plus
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2667089522000591
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author Rossella Bellini
Annalisa Moregola
Jasmine Nour
Yoann Rombouts
Olivier Neyrolles
Patrizia Uboldi
Fabrizia Bonacina
Giuseppe Danilo Norata
author_facet Rossella Bellini
Annalisa Moregola
Jasmine Nour
Yoann Rombouts
Olivier Neyrolles
Patrizia Uboldi
Fabrizia Bonacina
Giuseppe Danilo Norata
author_sort Rossella Bellini
collection DOAJ
description Background and aims: Atherogenesis results from altered lipid metabolism and impaired immune response. Emerging evidence has suggested that dendritic cells (DCs) participate to atherosclerosis-related immune response, but their impact is scarcely characterized. Clec4a4 or DCIR2 (Dendritic cell immunoreceptor 2) is a C-type lectin receptor, mainly expressed by CD8α− DCs, able to modulate T cell immunity. However, whether this DC subset could play a role in the atherogenesis is still poorly understood. Thus, the aim of this study is to investigate whether the absence of Clec4a4 could affect atherosclerosis-related immune response and atherosclerosis itself. Methods: Dcir2−/− Ldlr−/− and Ldlr−/− mice were fed a standard diet or cholesterol-enriched diet for 12 weeks. Subsequently, the profile of circulating and lymph nodes-resident immune cells was investigated together with the analysis of plasma lipid levels and atherosclerotic plaque extension in the aorta. Results: Here, we show that Clec4a4 expression is downregulated under hypercholesterolemia and its deficiency in Ldlr−/− mice results in the reduction of atherosclerotic plaque formation, together with altered lipid metabolism and impaired myeloid immune cell distribution. Conclusions: Our findings suggest a pro-atherosclerotic role of Clec4a4 in experimental atherosclerosis.
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spelling doaj.art-f2666e69875e4abe80fc3786cf0cd27b2023-03-21T04:17:16ZengElsevierAtherosclerosis Plus2667-08952023-03-0151812Dendritic cell marker Clec4a4 deficiency limits atherosclerosis progressionRossella Bellini0Annalisa Moregola1Jasmine Nour2Yoann Rombouts3Olivier Neyrolles4Patrizia Uboldi5Fabrizia Bonacina6Giuseppe Danilo Norata7Department of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyDepartment of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyDepartment of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyInstitut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, FranceInstitut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, FranceDepartment of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyDepartment of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyDepartment of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; Centro SISA per lo Studio dell’Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy; Corresponding author. Department of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.Background and aims: Atherogenesis results from altered lipid metabolism and impaired immune response. Emerging evidence has suggested that dendritic cells (DCs) participate to atherosclerosis-related immune response, but their impact is scarcely characterized. Clec4a4 or DCIR2 (Dendritic cell immunoreceptor 2) is a C-type lectin receptor, mainly expressed by CD8α− DCs, able to modulate T cell immunity. However, whether this DC subset could play a role in the atherogenesis is still poorly understood. Thus, the aim of this study is to investigate whether the absence of Clec4a4 could affect atherosclerosis-related immune response and atherosclerosis itself. Methods: Dcir2−/− Ldlr−/− and Ldlr−/− mice were fed a standard diet or cholesterol-enriched diet for 12 weeks. Subsequently, the profile of circulating and lymph nodes-resident immune cells was investigated together with the analysis of plasma lipid levels and atherosclerotic plaque extension in the aorta. Results: Here, we show that Clec4a4 expression is downregulated under hypercholesterolemia and its deficiency in Ldlr−/− mice results in the reduction of atherosclerotic plaque formation, together with altered lipid metabolism and impaired myeloid immune cell distribution. Conclusions: Our findings suggest a pro-atherosclerotic role of Clec4a4 in experimental atherosclerosis.http://www.sciencedirect.com/science/article/pii/S2667089522000591Clec4a4AtherosclerosisC-type lectin receptorsDendritic cellsImmune response
spellingShingle Rossella Bellini
Annalisa Moregola
Jasmine Nour
Yoann Rombouts
Olivier Neyrolles
Patrizia Uboldi
Fabrizia Bonacina
Giuseppe Danilo Norata
Dendritic cell marker Clec4a4 deficiency limits atherosclerosis progression
Atherosclerosis Plus
Clec4a4
Atherosclerosis
C-type lectin receptors
Dendritic cells
Immune response
title Dendritic cell marker Clec4a4 deficiency limits atherosclerosis progression
title_full Dendritic cell marker Clec4a4 deficiency limits atherosclerosis progression
title_fullStr Dendritic cell marker Clec4a4 deficiency limits atherosclerosis progression
title_full_unstemmed Dendritic cell marker Clec4a4 deficiency limits atherosclerosis progression
title_short Dendritic cell marker Clec4a4 deficiency limits atherosclerosis progression
title_sort dendritic cell marker clec4a4 deficiency limits atherosclerosis progression
topic Clec4a4
Atherosclerosis
C-type lectin receptors
Dendritic cells
Immune response
url http://www.sciencedirect.com/science/article/pii/S2667089522000591
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