Cxxc Finger Protein 1 Positively Regulates GM-CSF-Derived Macrophage Phagocytosis Through Csf2rα-Mediated Signaling

Abstract

Macrophages have a defensive function against bacteria through phagocytosis and the secretion of cytokines. Histone modifications play an essential role in macrophage functions. Here, we report that Cxxc finger protein 1 (CFP1), a key component of the SETD1 histone methyltransferase complex, promoted the phagocytic and bactericidal activity of GM-CSF-derived macrophages. CFP1-deficient mice were more susceptible to bacterial infection due to the decreased expression of Csf2rα, a subunit of the GM-CSF receptor essential for inflammation and alveolar macrophage development, through the loss of H3K4 modifications in the promoter of the Csf2rα gene. In addition, the lung tissues of CFP1-deficient mice exhibited spontaneous inflammatory symptoms, including both the infiltration of inflammatory cells and the accumulation of surfactant phospholipids and proteins. Furthermore, we showed that Csf2rα and PU.1 can partially rescue the defects in phagocytosis and in the intracellular killing of bacteria. Collectively, our data highlight the importance of CFP1 in the phagocytic and bactericidal activity of macrophages.

Analyzing the impact of CFP1 mutational landscape on epigenetic signaling

“…Taken together, these studies suggest that CFP1 is necessary for the function of HSCs and their progenitors. Other notable roles of CFP1 include B‐cell class switch DNA recombination, 26 T‐cell maturation, 27 and GM‐CSF‐derived macrophage phagocytic and bactericidal activity 28 . Collectively, these examples demonstrate the importance of CFP1 in several biological processes.…”

Codonopsis pilosula polysaccharides attenuate Escherichia coli-induced acute lung injury in mice

“…55 During bacterial infection, phagocytes such as macrophages can clear bacteria through phagocytosis, which includes the recognition, uptake, and degradation of bacteria. 56 In a mouse model of ARDS, an improvement of lung injury was observed when using murine alveolar macrophages previously cultured with mesenchymal stromal cell (MSC) extracellular vesicles and through the transference of MSC mitochondria to the macrophages, which is characterized by an enhancement of macrophage phagocytosis. 57 Our results indicated that CPPS could enhance intracellular killing and phagocytosis within macrophages at the indicated time points (Fig.…”

Epigenetic initiation of the T H 17 differentiation program is promoted by Cxxc finger protein 1

“…Clouaire et al (16) showed that Cxxc1 is required for H3K4me3 modification in embryonic stem cell, and Thomson et al (18) found a concordance of Cxxc1 binding with H3K4me3 and nonmethylated CGIs in mouse brain. Our recent studies also demonstrated that Cxxc1-dependent H3K4me3 plays a critical role in thymocyte development, phagocytosis, and the bactericidal activity of macrophages (19,20). However, the role of Cxxc1-mediated H3K4 trimethylation and DNA methylation in T H cells remains unclear.…”