Metabolic interaction between catecholamines and cholesterol derivatives is a potential mechanism for immune...

In recent years, the immunomodulatory role of adipose tissue (AT) has gained attention, yet the metabolic basis for immune homeostasis in AT remains unclear. Catecholamines (CAs) activate adipocyte β3-adrenergic receptors (β3-AR) to promote lipid metabolism, while cholesterol metabolism has bidirectional immunoregulatory properties. Whether the interaction between CAs and cholesterol regulates immune function in AT is unknown. Using chickens as models, we induced distinct immune states via dexamethasone (Dex) treatment and Newcastle disease virus (NDV) vaccination. Through qRT-PCR and metabolomics, we analyzed dynamic changes in lymphocytes, CAs, and cholesterol metabolism in AT. The results indicated that B cells were present in chicken AT and positively responded to different immune states through up-regulation. AT positively responded to Dex-induced immunosuppression (DIIS) and NDV-induced immune responses by altering cholesterol and CAs metabolisms. Moreover, the differences in cholesterol and CAs metabolisms were the key ways by which Dex affected immune response in AT. AT could synthesize bile acids and steroid derivatives, and secondary immunization possible was the key stage with active changes in cholesterol derivatives in AT. We identified a circuit pathway: "lymphocyte-catecholamine-adipocyte-cholesterol-cholesterol derivatives-lymphocyte," which may underpin immune microenvironment homeostasis in AT. Additionally, miR-206 was actively involved in the processes of DIIS, and the miR-206/MSMO1 pathway potentially regulated cholesterol metabolism in AT. This study provides a perspective for in-depth understanding of the immune regulation mechanism of AT and offer a direction for developing cholesterol derivatives for immune regulation.