Research
Both innate and adaptive immune responses have been involved in the initiation and progression of atherosclerosis and abdominal aortic aneurysm (AAA). However, there is currently no therapeutic strategy targeting the immune response in atherosclerosis and no medical therapy has been approved for the treatment of AAA.
We have shown that subpopulations of regulatory T (Treg) cells potently inhibit atherosclerotic lesion development and inflammation. We hypothesise that Treg cells and similarly, B cell type regulatory populations, have a broader role in the control of vascular inflammation and may significantly alter atherosclerosis or AAA development/progression. We will study in detail the mechanisms leading to recruitment of T and B cell subsets into the injured vessel wall and the pathways by which they modulate vascular inflammation. We will also develop novel immuno-modulatory and vaccination-based strategies to promote protective immune responses in atherosclerosis and AAA.
Publications
Basatemur GL, Jorgensen HF, Clarke MCH, Bennett MR, Mallat Z. Vascular smooth muscle cells in atherosclerosis. Nat Rev Cardiol. 2019 Jun 26. doi: 10.1038/s41569-019-0227-9.
Bagchi-Chakraborty J, Francis A, Bray T, Masters L, Tsiantoulas D, Nus M, Harrison J, Broekhuizen M, Leggat J, Clatworthy MR, Esp.li M, Smith KGC, Binder CJ, Mallat Z, Sage AP. B Cell Fcγ Receptor IIb Modulates Atherosclerosis in Male and Female Mice by Controlling Adaptive Germinal Center and Innate B-1-Cell Responses. Arterioscler Thromb Vasc Biol. 2019; 39:1379-1389.
Zhao TX, Mallat Z. Targeting the Immune System in Atherosclerosis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019; 73:1691-1706.
Clement M, Chappell J, Raffort J, Lareyre F, Vandestienne M, Taylor AL, Finigan A, Harrison J, Bennett MR, Bruneval P, Taleb S, J.rgensen HF, Mallat Z. Vascular Smooth Muscle Cell Plasticity and Autophagy in Dissecting Aortic Aneurysms. Arterioscler Thromb Vasc Biol. 2019; 39:1149-1159.
Paige E, Cl.ment M, Lareyre F, Sweeting M, Raffort J, Grenier C, Finigan A, Harrison J, Peters JE, Sun BB, Butterworth AS, Harrison SC, Bown MJ, Lindholt JS, Badger SA, Kullo IJ, Powell J, Norman PE, Scott DJA, Bailey MA, Rose-John S, Danesh J, Freitag DF, Paul DS, Mallat Z. Interleukin-6 Receptor Signaling and Abdominal Aortic Aneurysm Growth Rates. Circ Genom Precis Med. 2019; 12:e002413. doi: 10.1161/CIRCGEN.118.002413.
Sage AP, Tsiantoulas D, Binder CJ, Mallat Z. The role of B cells in atherosclerosis. Nat Rev Cardiol. 2019; 16:180-196.
Laurans L, Venteclef N, Haddad Y, Chajadine M, Alzaid F, Metghalchi S, Sovran B, Denis RGP, Dairou J, Cardellini M, Moreno-Navarrete JM, Straub M, Jegou S, McQuitty C, Viel T, Esposito B, Tavitian B, Callebert J, Luquet SH, Federici M, Fernandez-Real JM, Burcelin R, Launay JM, Tedgui A, Mallat Z, Sokol H, Taleb S. Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health. Nat Med. 2018; 24:1113-1120.
Tsiantoulas D, Sage AP, G.derle L, Ozsvar-Kozma M, Murphy D, Porsch F, Pasterkamp G, Menche J, Schneider P, Mallat Z, Binder CJ. BAFF Neutralization Aggravates Atherosclerosis. Circulation. 2018; 138:2263-2273.
Clement M, Haddad Y, Raffort J, Lareyre F, Newland SA, Master L, Harrison J, Ozsvar-Kozma M, Bruneval P, Binder CJ, Taleb S, Mallat Z. Deletion of IRF8 (Interferon Regulatory Factor 8)-Dependent Dendritic Cells Abrogates Proatherogenic Adaptive Immunity. Circ Res. 2018; 122:813-820.
Li X, Thome S, Ma X, Amrute-Nayak M, Finigan A, Kitt L, Masters L, James JR, Shi Y, Meng G, Mallat Z. MARK4 regulates NLRP3 positioning and inflammasome activation through a microtubuledependent mechanism. Nat Commun. 2017; 8:15986. doi: 10.1038/ncomms15986.
Sage AP, Nus M, Bagchi Chakraborty J, Tsiantoulas D, Newland SA, Finigan AJ, Masters L, Binder CJ, Mallat Z. X-Box Binding Protein-1 Dependent Plasma Cell Responses Limit the Development of Atherosclerosis. Circ Res. 2017; 121:270-281
Newland SA, Mohanta S, Cl.ment 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. Type-2 innate lymphoid cells control the development of atherosclerosis in mice. Nat Commun. 2017 Jun 7; 8:15781. doi: 10.1038/ncomms15781.
Nus M, Sage AP, Lu Y, Masters L, Lam BYH, Newland S, 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. Marginal zone B cells control the response of follicular helper T cells to a high-cholesterol diet. Nat Med. 2017; 23:601-610.
Metghalchi S, Ponnuswamy P, Simon T, Haddad Y, Laurans L, Cl.ment M, Dalloz M, Romain M, Esposito B, Koropoulis V, Lamas B, Paul JL, Cottin Y, Kotti S, Bruneval P, Callebert J, den Ruijter H, Launay JM, Danchin N, Sokol H, Tedgui A, Taleb S, Mallat Z. Indoleamine 2, 3-Dioxygenase Fine-Tunes Immune Homeostasis in Atherosclerosis and Colitis through Repression of Interleukin-10 Production. Cell Metab. 2015; 22:460-71.
Clement M, Basatemur G, Masters L, Baker L, Bruneval P, Iwawaki T, Kneilling M, Yamasaki S, Goodall J, Mallat Z. Necrotic Cell Sensor Clec4e Promotes a Proatherogenic Macrophage Phenotype Through Activation of the Unfolded Protein Response. Circulation. 2016; 134:1039-1051.
Sage AP, Mallat Z. Multiple potential roles for B cells in atherosclerosis. Ann Med. 2014 Aug;46(5):297-303. d
Ait-Oufella H, Sage AP, Mallat Z, Tedgui A. Adaptive (T and B cells) immunity and control by dendritic cells in atherosclerosis.
Circ Res. 2014 May 9;114(10):1640-60.
Li X, Deroide N, Mallat Z. The role of the inflammasome in cardiovascular diseases. J Mol Med (Berl). 2014 Apr;92(4):307-19
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. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nat Med. 2013 Oct;19(10):1273-80.
Deroide N, Li X, Lerouet D, Van Vré E, Baker L, Harrison J, Poittevin M, Masters L, Nih L, Margaill I, Iwakura Y, Ryffel B, Pocard M, Tedgui A, Kubis N, Mallat Z. MFGE8 inhibits inflammasome-induced IL-1β production and limits postischemic cerebral injury. J Clin Invest. 2013;123:1176-81.
Sage AP, Tsiantoulas D, Baker L, Harrison J, Masters L, Murphy D, Loinard C, Binder CJ, Mallat Z. BAFF Receptor Deficiency Reduces the Development of Atherosclerosis in Mice. Arterioscler Thromb Vasc Biol. 2012;32:1573-6.
Mallat Z, Lambeau G, Tedgui A. Lipoprotein-associated and secreted phospholipases A₂ in cardiovascular disease: roles as biological effectors and biomarkers. Circulation. 2010;122:2183-200.
Ait-Oufella H, Herbin O, Bouaziz JD, Binder CJ, Uyttenhove C, Laurans L, Taleb S, Van Vré E, Esposito B, Vilar J, Sirvent J, Van Snick J, Tedgui A, Tedder TF, Mallat Z. B cell depletion reduces the development of atherosclerosis in mice J Exp Med 2010 Aug 2; 207(8): 1579-87
Wang Y, Ait-Oufella H, Herbin O, Bonnin P, Ramkhelawon B, Taleb S, Huang J, Offenstadt G, Combadière C, Rénia L, Johnson JL, Tharaux PL, Tedgui A, Mallat Z TGF-β activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II-infused mice J Clin Invest 2010 120: 422-32
Taleb S, Romain M, Ramkhelawon B, Uyttenhove C, Pasterkamp G, Herbin O, Esposito B, Perez N, Yasukawa H, Van Snick J, Yoshimura A, Tedgui A, Mallat Z Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis J Exp Med 2009 206: 2067-77
