A polycomb group protein EED epigenetically regulates responses in lipopolysaccharide tolerized macrophages.

Background: To avoid exaggerated inflammation, innate immune cells adapt to become hypo-responsive or "tolerance" in response to successive exposure to stimuli, which is a part of innate immune memory. Polycomb repressive complex 2 (PRC2) mediates the transcriptional repression by catalyzing histone H3 lysine 27 trimethylation (H3K27me3) but little is known about its role in lipopolysaccharide (LPS)-induced tolerance in macrophages.

Result: We examined the unexplored roles of EED, a component of the PRC2, in LPS tolerant macrophages.

Loss of O-methylguanine DNA methyltransferase (MGMT) in macrophages alters responses to TLR3 stimulation and enhances DNA double-strand breaks and mitophagy.

O-methylguanine-DNA methyltransferase (MGMT) is a DNA damage repair enzyme. The roles of this enzyme in immune cells remain unclear. In this study, we explored the roles of MGMT in bone marrow-derived murine macrophages (BMMs) via the use of MGMT knockout (KO) mice.

O-methylguanine DNA methyltransferase regulates β-glucan-induced trained immunity of macrophages via farnesoid X receptor and AMPK.

Trained immunity is the heightened state of innate immune memory that enhances immune response resulting in nonspecific protection. Epigenetic changes and metabolic reprogramming are critical steps that regulate trained immunity. In this study, we reported the involvement of O-methylguanine DNA methyltransferase (MGMT), a DNA repair enzyme of lesion induced by alkylating agents, in regulation the trained immunity induced by β-glucan (BG).

Upregulation of programmed cell death 1 by interferon gamma and its biological functions in human monocytes.

Programmed cell death 1 (PD-1) is a co-inhibitory checkpoint receptor expressed in various immune cells, especially in activated T cells. Engagement of PD-1 with its ligand leads to the exhausted T cells and impaired antitumor immunity. To date, PD-1 expression and its roles have been widely reported in T cells but not well defined in innate immune cells including monocytes.