Postdoc Sam Keating and colleagues from the group of Niels Riksen, theme Vascular damage, revealed Set7 as a key regulator of trained immunity. Trained immunity describes the phenomenon that innate immune cells can develop a long-lasting pro-inflammatory phenotype following brief exposure to a micro-organism or microbial product. Using a combination of pharmacological and genetic approaches, they revealed a critical role for the histone methyltransferase Set7 in trained immunity. They have published their findings in Cell Reports.
Trained immunity confers a sustained augmented response of innate immune cells to a secondary challenge, via a process dependent on metabolic and transcriptional reprogramming. Previous research from the department of Internal Medicine showed that trained immunity can protect the host against recurrent infections, but can also contribute the pathophysiology in the context of chronic non-infectious inflammatory disorders, such as atherosclerosis. Because of its previous associations with metabolic and transcriptional memory, as well as the importance of H3 histone lysine 4 monomethylation (H3K4me1) to innate immune memory, they hypothesize that the Set7 methyltransferase has an important role in trained immunity induced by β-glucan. Using pharmacological studies of human primary monocytes, they identify trained immunity-specific immunometabolic pathways regulated by Set7, including a previously unreported H3K4me1-dependent plasticity in the induction of oxidative phosphorylation. This finding was validated in vivo in Set7 knock out mice in collaboration with their colleagues from Melbourne.
The identification of Set7 as a key enzyme in the development of innate immune memory provide a potential pharmacological target to modulate trained immunity.
Related news items
Dutch Cancer Society Grant received by Annemiek van Spriel and Laia Querol-Cano23 September 2020
Annemiek van Spriel and Laia Querol-Cano received a Dutch Cancer Society Grant of 707,298 euros to study the cancer cell surface in immunotherapy.read more
Frank Walboomers 25-years work anniversary at Radboudumc17 September 2020
Frank Walboomers, associate professor at the research group Regenerative Biomaterials at the Dept. of Dentistry (theme Reconstructive & Regenerative Medicine), celebrated his 25th work anniversary at Radboudumc.read more
Tjitske Kleefstra appointed endowed professor of Clinical genetics and psychopathology of rare syndromes17 September 2020
Tjitske Kleefstra has been appointed endowed professor of Clinical genetics and psychopathology of rare syndromes at the department of Neurodevelopmental disorders, with effect from 1 September.read more
Annette Schenck appointed professor of Translational Genetics17 September 2020
Annette Schenck has been appointed professor of Translational Genetics at the department of Neurodevelopmental disorders, with effect from 1 August. The chair will bring together fundamental and translational research in the field of brain developmental disorders.read more
Centuries-old medicine reduces the risk of new cardiovascular disease in heart patients17 September 2020
Colchicine, an anti-inflammatory drug that has been used for gout for centuries, has been shown to prevent cardiovascular disease in patients who have had a heart attack or are suffering from narrowed coronary arteries. Results of the study are published in the New England Journal of Medicine.read more