Figure 8.

Summary schematic of the different roles of mineralocorticoid receptor (MR) in modulating the development and function of macrophages in zebrafish. A reduction in MR signalling in zebrafish, either through genetic perturbations or pharmacological antagonism, leads to altered macrophage responsivity to developmental and inflammatory signals, showing that MR is crucial for macrophage development and function. (A) During a key developmental period (0-120 hours postfertilization [hpf]), larvae lacking MR (MRKO) experience a global reduction in whole-body macrophage numbers. This is associated with a lack of production in the yolk and distribution out of the yolk, and these macrophages show reduced transcript abundance of the colony-stimulating factor receptor 1 (csfr1a) gene, which encodes a receptor critical for early macrophage migration out of the yolk. In addition, these macrophages are more susceptible to apoptotic cell death. (B) MRKO macrophages show increased responsivity to inflammatory signals (eg, after tail wounding) associated with increased levels of C-C chemokine receptor 2 (ccr2) gene expression. (C) When WT larvae are treated with the MR antagonist eplerenone between 2 and 120 hpf, the global reduction in macrophage number that is observed in MRKO larvae (panel A) is phenocopied. (D) Eplerenone treatment over 6 hours (short-term), results in a reduced responsivity of macrophages to inflammatory signals, which is associated with a reduction in ccr2 expression in macrophages. This is in sharp contrast to the increased responsivity that is observed in MRKO larvae (panel B). Image created using Biorender.com.