TREM2 limits necrotic core formation during atherogenesis by controlling macrophage survival and efferocytosis

Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries [[1][1]], [[2][2]], and its main complications, myocardial infarction and stroke, are the leading cause of mortality worldwide [[3][3]]. Recent studies have identified Triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating several key myeloid cell functions [[4][4]], as a highly expressed marker of macrophage foam cells in experimental and human atherosclerosis [[5][5]]. However, the function of TREM2 in the development of atherosclerosis is unknown. Here, we show that hematopoietic or global TREM2 deficiency increases necrotic core formation in early experimental atherosclerosis. We further demonstrate that TREM2 is essential for the efferocytosis capacities of macrophages, and to the survival of lipid-laden macrophages, altogether indicating a crucial role of TREM2 in maintaining the balance between foam cell death and their clearance in atherosclerotic lesions, thereby controlling plaque necrosis. ### Competing Interest Statement Christian Haass is a collaborator of Denali Therapeutics, participated on one advisory board meeting of Biogen and received a speaker honorarium from Novartis and Roche. Christian Haass is a member of the advisory board of AviadoBio. Other authors have no conflict of interest to declare. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-4 [5]: #ref-5