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News: EAS Academy - Lecture of the week

The immune system: The next game-changer?

Monday 20 April 2020   (0 Comments)
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About the presenter: Professor Matthias Nahrendorf

Matthias Nahrendorf, MD PhD, is a Professor at Harvard Medical School and a Principal Investigator at the MGH Center for Systems Biology. He studies the function, supply and production of leukocytes, and the signals that regulate hematopoiesis after injuries such as myocardial infarction or stroke. He described that after MI, the spleen releases a large population of ready-made leukocytes that travel to the ischemic heart (Science 2009).

He further found that MI and chronic stress increases sympathetic nerve activity in the bone marrow. This modulates the hematopoietic stem cell niche, activating migration and proliferation of myeloid progenitor cells (Nature 2012, Nat Med 2014). Resident macrophages, on the other hand, do not derive from circulating cells and promote steady state functions such as cardiac conduction (Cell 2017). The laboratory also develops and employs imaging to sample biology non-invasively, using MR, nuclear, optical and microscopic modalities.
Dr. Nahrendorf is an editorial board member of the European Heart Journal, JACC, Circ Res, ATVB, Circulation, Cardiovascular Research and The Journal of Nuclear Medicine. He published >200 peer reviewed articles, was given the MGH Research Scholar Award in 2014, the Basic research Award of the German Society of Cardiology in 2015 and the NHLBI Outstanding Investigator Award in 2018.

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About the topic

Development of atherogenesis involves a complex interplay between lipids, inflammatory stress and cellular immune responses. Circulating monocytes have been shown to have a pivotal role in plaque inflammation, infiltrating the plaque where they differentiate into macrophages, and further exacerbate the inflammatory environment. Recent studies have implicated that the ‘neural-hematopoietic’ inflammatory axis as a key driver of atherogenesis. Imaging approaches may hold the key to understanding vascular changes in the bone marrow during acute inflammation and help to identify novel therapeutic targets.
Monocytes and monocyte-derived macrophages also play a key role in the immune response to cardiac ischaemia associated with myocardial infarction (MI). In particular, pro-inflammatory monocytes dominate the early acute period after MI, with neutrophils the first immune cells present at the site of injury in response to danger-associated molecules released by necrotic tissue. Although neutrophils initially help to clear cellular debris, their inflammatory mediators can lead to tissue damage and further leucocyte recruitment. Monocytes and monocyte-derived macrophages release inflammatory cytokines, proteases, and reactive oxygen which together perpetuate inflammation. There is emerging evidence, however, that neutrophils may also have a protective role in MI, as the lack of neutrophil -derived mediators impacts the ability of cardiac macrophages to clear cellular debris, and promotes a reparative phenotype. Identification of novel targets that restrict the local inflammatory monocyte response and potentiate cardioprotective properties may offer therapeutic potential for immunomodulatory approaches to healing post-MI.

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Key references

Vandoorne K, Rohde D, Kim HY, Courties G, Wojtkiewicz GR, Honold L, Hoyer FF, Frodermann V, Nayar R, Herisson FE, Jung Y, Désogère P, Vinegoni C, Caravan P, Weissleder R, Sosnovik DE, Lin CP, Swirski FK, Nahrendorf M. Imaging the vascular bone marrow niche during inflammatory stress. Circ Res 2018; doi: 10.1161/CIRCRESAHA.118.313302. [Epub ahead of print]
Honold L, Nahrendorf M. Resident and monocyte-derived macrophages in cardiovascular disease. Circ Res 2018; 122:113-27.
Hoogeveen RM, Nahrendorf M, Riksen NP, Netea MG, de Winther MPJ, Lutgens E, Nordestgaard B, Neidhart M, Stroes ESG, Catapano AL, Bekkering S. Monocyte and haematopoietic progenitor reprogramming as common mechanism underlying chronic inflammatory and cardiovascular diseases. Eur Heart J 2017 doi: 10.1093/eurheartj/ehx581. [Epub ahead of print]

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