PRE2023-REPROGRAMACION TRANSCRIPCIONAL DEL RECEPTOR NUCLEAR LXRALFA Y EL CONTROL DE LA IDENTIDAD DE LOS MACROFAGOS EN HOMEOSTASIS E INFLAMACION-PID2022-137696OB-I00

Macrophages are one of the most abundant leukocyte populations in our organism and present a great functional diversity in tissues. To understand how macrophage behavior is regulated, we study the functions of macrophages through transcriptional regulation by nuclear receptors, a type of transcription factors that control gene expression. This proposal studies the functions of macrophages in different tissues and situations, through the control of their activities exerted at the transcriptional level by the nuclear receptor Liver X Receptor (LXRa). This project is oriented towards the cellular and molecular study of LXRa in macrophages, through in vitro and in vivo studies with mouse models of LXRa deficiency, and "knockin" transgenic. Our recent results suggest that LXRa exhibits a dual role in macrophages. On one hand, in healthy tissues it exerts homeostatic functions in certain subtypes of resident macrophages, controlling the development of macrophage subtypes. On the other hand, in inflammatory conditions, LXRa promotes antimicrobial actions in recruited macrophages. Using genomic strategies we will search for the genome-wide localization of LXRalpha, and we will analyze by proteomic approaches the molecular interactions of LXRalpha in different situations. The second goal will analyze the function of LXRalpha in macrophages in inflammation. We hope that our contribution can be transferred to possible future strategies for therapeutic intervention.