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Dr Stephen Newland

Research Associate


Research Interests

How ILC2 coordinate inflammation and healing in cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of death worldwide, increasing in incidence year on year to become accountable for 1 in 4 deaths globally in 2010 [1]. Atherosclerosis is a component of CVD where deposits of low density lipoprotein in the arterial wall lead to the infiltration of immune cells, inflammation and growth of plaques. This process can culminate in occlusion of the artery or plaque rupture and thrombosis. How the lesion matures is influenced by the populations of infiltrating innate and adaptive immune cells, their activation state and how they communicate with the non-immune cells in the surrounding arterial tissue.

Innate Lymphoid Cells (ILC) are a rare population morphologically similar to lymphocytes which secrete large amounts of the type II cytokines IL-4, IL-5 and IL-13. However, unlike T or B cells they do not express recombined antigen receptors such as the TCR and BCR. In our earlier work we identified how a population of ILC2 in close proximity to developing atheroma modified the infiltrating macrophage phenotype, reducing local inflammation and aiding wound healing. This was then subsequently shown to be downstream of IL-13 secreted by the ILC2.

More recently we have moved towards understanding novel mechanisms of ILC2 activation during atherosclerosis, how these cells can also influence the wound healing process after experimental myocardial infarction as well as the changing population dynamics in human subjects during low dose IL2 clinical trials.

My work is funded by the British Heart Foundation (BHF)

Keywords

immunometabolism ; ILC2 ; atherosclerosis ; innate immunity ; Immuno-modulation ; Type II innate immune cells ; inflammation ; myocardial infarction

Collaborators outside this directory

Key Publications

Interleukin-33 Signaling Controls the Development of Iron-Recycling Macrophages. Lu Y, Basatemur G, Scott IC, Chiarugi D, Clement M, Harrison J, Jugdaohsingh R, Yu X, Newland SA, Jolin HE, Li X, Chen X, Szymanska M, Haraldsen G, Palmer G, Fallon PG, Cohen ES, McKenzie ANJ, Mallat Z.Immunity. 2020 May 19;52(5):782-793.e5. doi: 10.1016/j.immuni.2020.03.006. Epub 2020 Apr 8.PMID: 32272082

2019 ATVB Plenary Lecture: Interleukin-2 Therapy in Cardiovascular Disease: The Potential to Regulate Innate and Adaptive Immunity. Zhao TX, Newland SA, Mallat Z.Arterioscler Thromb Vasc Biol. 2020 Apr;40(4):853-864. doi: 10.1161/ATVBAHA.119.312287. Epub 2020 Feb 6.PMID: 32078364 Review

MARK4 (Microtubule Affinity-Regulating Kinase 4)-Dependent Inflammasome Activation Promotes Atherosclerosis-Brief Report.Clement M, Chen X, Chenoweth HL, Teng Z, Thome S, Newland SA, Harrison J, Yu X, Finigan AJ, Mallat Z, Li X.Arterioscler Thromb Vasc Biol. 2019 Aug;39(8):1645-1651. doi: 10.1161/ATVBAHA.119.312478. Epub 2019 Jun 6.PMID: 31167564

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.

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. 201723(5):601-610

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