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

Frontiers in Immunology
Zhaoyuan HuiLie Wang

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.

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Citations

Sep 10, 2019·Cancer Cell International·Jingyue SunShuang Liu
Jul 29, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yidai YangJean-Francois Couture
Dec 23, 2021·Immunological Reviews·Atsushi OnoderaToshinori Nakayama

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Methods Mentioned

BETA
acetylation
RNA-seq
flow cytometry
Immunoprecipitation
ChIP
Confocal microscopy
cDNA
PCR
bronchoalveolar lavage
transfection

Software Mentioned

Zeiss ZEN
DAVID
Hierarchical Indexing for Spliced Alignment of Transcripts ( H...

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