BHF Intermediate Research Fellow
Adaptive Immune responses and Atherosclerosis
I am investigating how different subsets of B cells regulate the development of atherosclerosis, in order to understand if immune therapies could slow or stabilise disease progression.
Atherosclerosis is a complex disease with many contributing networks, including vessel wall inflammation, metabolism and the recruitment and activation of innate and adaptive immune systems.
Contrary to long-standing views, not all B cells play a protective, anti-atherogenic role. The identification of the diversity of B cell subsets and B cell functions means there may be multiple, potentially antagonistic, pathways by which B cells are involved in plaque development.
Therefore, we are interrogating the mechanisms of B cell action and the subtypes of B cells that may be involved. We are also interested in how the BAFF family of ligands and receptors are involved in cardiovascular disease.
We believe this research can lead to modification of current treatments used in other diseases to treat heart disease and stroke, may reveal novel pathways promoting atherosclerosis that could be targeted by new treatments and aid in understanding the links between autoimmune diseases and cardiovascular risk.
B cells ; immune tolerance ; atherosclerosis ; adaptive immunity ; antigen presentation
Collaborators outside this directory
- Dr Menna Clatworthy - http://www.med.cam.ac.uk/clatworthy/
- Dr Pasquale Maffia - http://www.gla.ac.uk/researchinstitutes/iii/staff/pasqualemaffia/
- Professor Christoph Binder - http://www.meduniwien.ac.at/hp/phd-mst/research-labs/christoph-j-binder-md-phd/
Regulatory B cell-specific interleukin-10 is dispensable for atherosclerosis development in mice. Sage AP, Nus M, Baker LL, Finigan AJ, Masters LM, Mallat Z. Arterioscler Thromb Vasc Biol. 2015 Aug;35(8):1770-3.
Targeting B Cells in Atherosclerosis: Closing the Gap From Bench to Bedside. Tsiantoulas D, Sage AP, Mallat Z, Binder CJ. Arterioscler Thromb Vasc Biol. 2014 Oct 30.
MHC Class II-restricted antigen presentation by plasmacytoid dendritic cells drives proatherogenic T cell immunity. Sage AP, Murphy D, Maffia P, Masters LM, Sabir SR, Baker LL, Cambrook H, Finigan AJ, Ait-Oufella H, Grassia G, Harrison JE, Ludewig B, Reith W, Hansson GK, Reizis B, Hugues S, Mallat Z. Circulation. 2014 Oct 14;130(16):1363-73.
Deletion of chromosome 9p21 noncoding cardiovascular risk interval in mice alters smad2 signaling and promotes vascular aneurysm. Loinard C, Basatemur G, Masters L, Baker L, Harrison J, Figg N, Vilar J, Sage AP, Mallat Z. Circ Cardiovasc Genet. 2014 Dec;7(6):799-805.
Multiple potential roles for B cells in atherosclerosis. Sage AP, Mallat Z. Ann Med. 2014 Aug;46(5):297-303.
Adaptive (T and B cells) immunity and control by dendritic cells in atherosclerosis. Ait-Oufella H, Sage AP, Mallat Z, Tedgui A. Circ Res. 2014 May 9;114(10):1640-60.
Sialyltransferase activity and atherosclerosis. Sage AP, Mallat Z. Circ Res. 2014 Mar 14;114(6):935-7.
B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Zouggari Y, Ait-Oufella H, Bonnin P, Simon T, Sage AP, Guérin C, Vilar J, Caligiuri G, Tsiantoulas D, Laurans L, Dumeau E, Kotti S, Bruneval P, Charo IF, Binder CJ, Danchin N, Tedgui A, Tedder TF, Silvestre JS, Mallat Z. Nat Med. 2013 Oct;19(10):1273-80.
BAFF receptor deficiency reduces the development of atherosclerosis in mice--brief report. Sage AP, Tsiantoulas D, Baker L, Harrison J, Masters L, Murphy D, Loinard C, Binder CJ, Mallat Z. Arterioscler Thromb Vasc Biol. 2012 Jul;32(7):1573-6.
Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids. Sage AP, Lu J, Atti E, Tetradis S, Ascenzi MG, Adams DJ, Demer LL, Tintut Y. J Bone Miner Res. 2011 Jun;26(6):1197-206.
Hyperphosphatemia-induced nanocrystals upregulate the expression of bone morphogenetic protein-2 and osteopontin genes in mouse smooth muscle cells in vitro. Sage AP, Lu J, Tintut Y, Demer LL. Kidney Int. 2011 Feb;79(4):414-22.
Regulatory mechanisms in vascular calcification. Sage AP, Tintut Y, Demer LL. Nat Rev Cardiol. 2010 Sep;7(9):528-36.