Emerging Roles for G-protein Coupled Receptors in Development and Activation of Macrophages.

Xinming Wang,Abishek Iyer,Heinrich Körner,Wei Wei,A Bruce Lyons

doi:10.3389/fimmu.2019.02031

Abstract

Macrophages have emerged as a key component of the innate immune system that emigrates to peripheral tissues during gestation and in the adult organism. Their complex pathway to maturity, their unique plasticity and their various roles as effector and regulatory cells during an immune response have been the focus of intense research. A class of surface molecules, the G-Protein coupled receptors (GPCRs) play important roles in many immune processes. They have drawn attention in regard to these functions and the potential for therapeutic targets that can modulate the response of immune cells in pathologies such as diabetes, atherosclerosis, and chronic inflammatory diseases. Of the more than 800 GPCRs identified, ~100 are currently targeted with drugs which have had their activity investigated in vivo. Macrophages express a number of GPCRs which have central roles during cell differentiation and in the regulation of their functions. While some macrophage GPCRs such as chemokine receptors have been studied in great detail, the roles of other receptors of this large family are still not well understood. This review summarizes new insights into macrophage biology, differences of human, and mouse macrophages and gives details of some of the GPCRs expressed by this cell type.

Highlights

Inflammation is a highly complex protective response of the mammalian immune system that is initiated at sites of infection or injury
The complexity of the possible functional interactions of these monocyte/macrophage receptors with the micro- and macroenvironment is elevated by various factors
While reductionistic in vitro approaches have been able to form a picture of specific gene signatures of macrophage populations after stimulation with opposing cytokines such as GM-CSF and CSF-1 or IL-4 and IFN-γ [32, 36] it is highly unlikely that under inflammatory conditions in vivo equivalent populations can develop in adjacent tissue areas depending on the respective conditions

Summary

Introduction

Inflammation is a highly complex protective response of the mammalian immune system that is initiated at sites of infection or injury. The main goal of this process is to remove the danger stimulus and damaged cells, resolve inflammation, and support a repair of the damaged tissue. If this process that is normally targeted at an infectious stimuli or injured tissue remains unresolved, innate immune activation can be prolonged and become misdirected at healthy cells leading to chronic inflammation and disease [1]. Central to the inflammatory response and its regulation is the cellular innate immune response that in its early stages encompasses an initial neutrophil influx into the tissue followed by an immigration of monocytes and cells of the adaptive immune system. Macrophages respond strongly and early to antigenic challenges in the tissue and the

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