Triggering receptor expressed on myeloid Cells-2 (TREM2) inhibits steroidogenesis in adrenocortical cell by macrophage-derived exosomes in lipopolysaccharide-induced septic shock

Endogenously produced glucocorticoids exhibit immunomodulating properties and are of pivotal importance for sepsis outcome. Uncontrolled activation the immune-adrenal crosstalk increases risk sepsis-related death. Triggering receptor expressed on myeloid cells-2 (TREM2) is richly macrophages has been demonstrated to improve outcome by enhancing elimination pathogens. However, role mode action macrophage TREM2 adrenocortical steroidogenesis remains unclear in septic shock. The acute shock model was established intraperitoneally challenging wild-type (WT) knock-out (Trem2?/?) mice with lipopolysaccharide (LPS, 30 mg/kg). were assessed expression local inflammation adrenal gland synthesis corticotropin releasing hormone (CRH) adrenocorticotropic (ACTH) vivo. Bone marrow-derived or macrophage-derived exosomes isolated from WT Trem2?/? co-cultured cells. steroidogenic enzymes corticosterone production assessed. Genetic deficiency caused significantly higher levels at early stage LPS-induced shock; whereas neither increased CRH ACTH nor exacerbated tissue during Ex vivo study revealed that promoted corticosterone. Furthermore, able mimic steroidogenesis. At shock, biosynthesis can be inhibited cells, which might partially associate exosomes.