RESUMO
Stress exposure has been shown to modulate innate and adaptive immune responses. Indeed, stress favors myelopoiesis and monocyte generation and contributes to cardiovascular disease development. As sex hormones regulate innate and adaptive immune responses, we decided to investigate whether stress exposure leads to a different immune response in female and male mice. Our data demonstrated that psychosocial stressinduced neutrophilia in male, but not female mice. Importantly, we identified that B-cell numbers were reduced in female, but not male mice upon exposure to stress. Thus, our study revealed that the stress-induced immune alterations are sex-dependent, and this is an important feature to consider for future investigations.
RESUMO
Atherosclerosis is driven by the expansion of cholesterol-loaded 'foamy' macrophages in the arterial intima. Factors regulating foamy macrophage differentiation and survival in plaque remain poorly understood. Here we show, using trajectory analysis of integrated single-cell RNA sequencing data and a genome-wide CRISPR screen, that triggering receptor expressed on myeloid cells 2 (Trem2) is associated with foamy macrophage specification. Loss of Trem2 led to a reduced ability of foamy macrophages to take up oxidized low-density lipoprotein (oxLDL). Myeloid-specific deletion of Trem2 showed an attenuation of plaque progression, even when targeted in established atherosclerotic lesions, and was independent of changes in circulating cytokines, monocyte recruitment or cholesterol levels. Mechanistically, we link Trem2-deficient macrophages with a failure to upregulate cholesterol efflux molecules, resulting in impaired proliferation and survival. Overall, we identify Trem2 as a regulator of foamy macrophage differentiation and atherosclerotic plaque growth and as a putative therapeutic target for atherosclerosis.
