Neil MacRitchie1, Gianluca Grassia1, Jonathan Noonan1, Jennifer E Cole2, Catherine E Hughes1, Juliane Schroeder1, Robert A Benson1, Clement Cochain3, Alma Zernecke3, Tomasz J Guzik4,5, Paul Garside1, Claudia Monaco2, Pasquale Maffia1,4,6. 1. Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK. 2. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK. 3. Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany. 4. Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. 5. Department of Internal Medicine, Jagiellonian University, Collegium Medicum, Kraków, Poland. 6. Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy.
Abstract
AIMS: Aortic adaptive immunity plays a role in atherosclerosis; however, the precise mechanisms leading to T-cell activation in the arterial wall remain poorly understood. METHODS AND RESULTS: Here, we have identified naïve T cells in the aorta of wild-type and T-cell receptor transgenic mice and we demonstrate that naïve T cells can be primed directly in the vessel wall with both kinetics and frequency of T-cell activation found to be similar to splenic and lymphoid T cells. Aortic homing of naïve T cells is regulated at least in part by the P-selectin glycosylated ligand-1 receptor. In experimental atherosclerosis the aorta supports CD4+ T-cell activation selectively driving Th1 polarization. By contrast, secondary lymphoid organs display Treg expansion. CONCLUSION: Our results demonstrate that the aorta can support T-cell priming and that naïve T cells traffic between the circulation and vessel wall. These data underpin the paradigm that local priming of T cells specific for plaque antigens contributes to atherosclerosis progression.
AIMS: Aortic adaptive immunity plays a role in atherosclerosis; however, the precise mechanisms leading to T-cell activation in the arterial wall remain poorly understood. METHODS AND RESULTS: Here, we have identified naïve T cells in the aorta of wild-type and T-cell receptor transgenic mice and we demonstrate that naïve T cells can be primed directly in the vessel wall with both kinetics and frequency of T-cell activation found to be similar to splenic and lymphoid T cells. Aortic homing of naïve T cells is regulated at least in part by the P-selectin glycosylated ligand-1 receptor. In experimental atherosclerosis the aorta supports CD4+ T-cell activation selectively driving Th1 polarization. By contrast, secondary lymphoid organs display Treg expansion. CONCLUSION: Our results demonstrate that the aorta can support T-cell priming and that naïve T cells traffic between the circulation and vessel wall. These data underpin the paradigm that local priming of T cells specific for plaque antigens contributes to atherosclerosis progression.
Authors: Agnieszka Sagan; Tomasz P Mikolajczyk; Wojciech Mrowiecki; Neil MacRitchie; Kevin Daly; Alan Meldrum; Serena Migliarino; Christian Delles; Karol Urbanski; Grzegorz Filip; Boguslaw Kapelak; Pasquale Maffia; Rhian Touyz; Tomasz J Guzik Journal: Front Immunol Date: 2019-09-04 Impact factor: 7.561
Authors: Monika Sharma; Martin P Schlegel; Milessa S Afonso; Emily J Brown; Karishma Rahman; Ada Weinstock; Brian E Sansbury; Emma M Corr; Coen van Solingen; Graeme J Koelwyn; Lianne C Shanley; Lauren Beckett; Daniel Peled; Juan J Lafaille; Matthew Spite; P'ng Loke; Edward A Fisher; Kathryn J Moore Journal: Circ Res Date: 2020-04-27 Impact factor: 17.367
Authors: Laura Ospina-Quintero; Julio C Jaramillo; Jorge H Tabares-Guevara; José R Ramírez-Pineda Journal: Front Immunol Date: 2020-04-24 Impact factor: 7.561