GATA6+ Peritoneal Resident Macrophage: The Immune Custodian in the Peritoneal Cavity

Abstract

Peritoneal resident macrophages (PRMs) have been a prominent topic in the research field of immunology due to their critical roles in immune surveillance in the peritoneal cavity. PRMs initially develop from embryonic progenitor cells and are replenished by bone marrow origin monocytes during inflammation and aging. Furthermore, PRMs have been shown to crosstalk with other cells in the peritoneal cavity to control the immune response during infection, injury, and tumorigenesis. With the advance in genetic studies, GATA-binding factor 6 (GATA6) has been identified as a lineage determining transcription factor of PRMs controlling the phenotypic and functional features of PRMs. Here, we review recent advances in the developmental origin, the phenotypic identity, and functions of PRMs, emphasizing the role of GATA6 in the pathobiology of PRMs in host defense, tissue repairing, and peritoneal tumorigenesis.

Keywords: GATA6; host defense; peritoneal resident macrophage; peritoneal tumorigenesis; tissue injury.

FIGURE 1

Schematics show the regulation of GATA6 in PRMs. 1) Histone lysine methylation (H3K4me3) modification at the GATA6 locus in PRMs facilitates active GATA6 transcription. 2) Stromal cells express Wilms’ Tumor 1(WT1) transcription factor for retinal dehydrogenase 1 and 2 enzymes that convert retinol to Retinoidc acid (RA). To induce GATA6 transcription in PRM, Retinoid acid receptor β (RARβ) needs to be activated by RA, and both RARβ and retinoid X receptor (RXR) need to bind retinoic acid response elements (RAREs). 3) Other retinoic acid receptors (RARα and RARγ) induced by yet unidentified stimuli at PRMs also collaborates with the RA-driven GATA6 transcription.