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Dr Andrew Sage

Dr Andrew Sage

BHF Intermediate Research Fellow


Research Interests

Understanding the pathogenic role of B cells in Atherosclerosis

Atherosclerosis, a major underlying cause of cardiovascular disease, is driven by lipid accumulation in the vascular wall. The chronic response to injury and invading immune response is complex, but understanding this is critical to identifying and treating the most vulnerable patients.

Trapped lipids and uncleared dying cells within atherosclerotic plaques are recognised by antibodies produced by the B cell system. I am trying to unravel the distinct roles of different types of antibodies as well as distinct functions of B cells now recognised to play important roles in adaptive immune responses. Beyond helping to understand the pathobiology of atherosclerosis, our studies also aim to better understand the causal links between autoimmune diseases and cardiovascular disease. In particular, autoimmune diseases (and cancers) are already being treated with B cell depleting therapies for which the impacts on cardiovascular risk are only beginning to be understood.

Recently, our lab defined the direct overall contribution of endogenous antibodies to atherosclerosis in a fully immunocompetent model. Ongoing projects include understanding the role of specific types of B cell activation, the role of IgG receptors and the impact of targeting the BAFF family of B cell-regulating cytokines.

Keywords

B cells ; immune tolerance ; atherosclerosis ; adaptive immunity ; antigen presentation

Collaborators outside this directory

Key Publications

X-box Binding Protein-1 dependent Plasma Cell Responses Limit the Development of Atherosclerosis. Sage AP, Nus M, Bagchi Chakraborty J, Tsiantoulas D, Newland SA, Finigan AJ, Masters L, Binder CJ, Mallat Z. Circ Res 2017. Online.

Type-2 innate lymphoid cells control the development of atherosclerosis in mice. Newland SA, Mohanta S, Clément M, Taleb S, Walker JA, Nus M, Sage AP, Yin C, Hu D, Kitt LL, Finigan AJ, Rodewald HR, Binder CJ, McKenzie ANJ, Habenicht AJ, Mallat Z. Nat Commun 2017. 8:15781.

Readapting the adaptive immune system – Therapeutic approaches for atherosclerosis. Sage AP and Mallat Z. Br J Pharmacol 2017. Online.

Marginal zone B cells control follicular helper T cell response to high cholesterol diet.  Nus M, Sage AP, Lu Y, Masters L, Lam BYH, Newland SA, Weller S, Tsiantoulas D, Raffort J, Marcus D, Finigan A, Kitt L, Figg N, Schirmbeck R, Kneilling M, Yeo GSH, Binder CJ, de la Pompa JL, Mallat Z. Nat Med. 2017. 23(5):601-610

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.

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.

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