Guiding macrophages to resolution: insights into the transcriptional pro-resolving mechanisms

Abstract

The inflammatory response is a tightly regulated process, which is essential for maintaining immune homeostasis. When this regulation is out of balance, persistence of the inflammatory response can lead to the development of (chronic) inflammatory diseases. Macrophages play a central role in this balance due to their phenotypic plasticity, allowing them to promote both pro-inflammatory and pro resolving processes. Current therapeutic strategies predominantly focus on how to dampen the inflammatory response to induce resolution of inflammation. However, resolution is not just the disappearance of inflammatory signaling, but rather an actively regulated process. Here, we review the current understanding of pro-resolving signaling pathways in macrophages and how negative regulation of pro-inflammatory pathways promote resolution. Furthermore, we highlight the importance of the environment and discuss the role of specialized pro-resolving lipid mediators to promote the macrophage conversion towards a more pro-resolving phenotype. This knowledge functions as basis for the development of new therapeutic strategies to treat inflammatory diseases by promoting pro-resolving signaling in macrophages. Nanoparticles present as promising carrier for these pro-resolving drugs to target specifically macrophages at sites of inflammation, restoring the macrophage disbalance and promoting immune homeostasis.