In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. suppl_1 ( 2016-05)
Abstract:
Background: Adaptive immunity and co-stimulatory signals are pivotal to all stages of atherosclerosis. CD40-CD40L (CD154) co-stimulatory molecules are central mediators of disease progression. However, it remains undetermined whether platelet- or T cell-specific CD40L contributes to its pro-atherogenic function. Method: We generated mice carrying a mutated allele of the CD40L gene flanked by loxp-sites sensitive to cre-mediated inactivation. We crossed these to Apoe -/- -deficient mice which also expressed Cre specifically in T cells ( Cd4Cre tg ) or platelets (Pf4Cre tg ) to generate Apoe -/- Cd40lg fl/fl -Cd4Cre tg , -Cd4Cre wt , -Pf4Cre tg , or -Pf4Cre wt mice. After consuming chow diet for 28 weeks the immune status and atherosclerosis was assessed by flow cytometry, RNA expression analysis and histology of the ascending aorta, blood, draining lymph nodes, and spleen. Results: Specific deletion of CD40L on T cells leads to decreased atherosclerotic lesion size in the ascending aorta while plaque size in Apoe -/- Cd40lg fl/fl -Pf4Cre tg or -Pf4Cre wt mice did not differ. Furthermore, platelet-specific ablation of CD40L did not results in changes of immune cells distribution. In contrast, cytokine and RNA analysis data pointed to a less inflammatory phenotype in Apoe -/- Cd40lg fl/fl Cd4Cre tg mice compared to Apoe -/- Cd40lg fl/fl Cd4Cre wt controls. Interestingly, T cell-specific inactivation of CD40L also caused a systemic decrease of Tregs in draining lymph nodes, spleen, blood, and thymus. Conclusion: Taken together our data confirm that CD40L expressed on T cells but not on platelets contributes to the disease-aggravating role of the CD40/CD40L dyad in atherosclerosis. Thus, T cell-expressed CD40L may provide a promising candidate for further investigation in atherosclerosis and other inflammatory diseases.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.36.suppl_1.240
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2016
detail.hit.zdb_id:
1494427-3
Bookmarklink