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TREM‐2, an innate immune receptor, is dependent on C/EBPalpha and PU.1 transcription factors during the differentiation of hematopoietic stem cells to macrophages
Author(s) -
MANCARELLI M.MICHELA,
Derossi Charles,
Torbett Bruce E
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.833.19
Subject(s) - innate immune system , biology , haematopoiesis , microbiology and biotechnology , cebpa , myeloid , macrophage , inflammation , immune system , receptor , stem cell , immunology , transcription factor , in vitro , gene , genetics
Triggering receptor on myeloid cells‐2 (TREM‐2) is a member of the innate immune signaling receptor TREM family, reportedly only expressed on macrophages, dendritic cells, microglia, but not on monocytes. TREM‐2 is necessary for regulation of macrophage activation, and loss of TREM‐2 results in a decrease of phagocytosis and an inability to control inflammatory mediators. Since little is known about TREM‐2 gene expression during human stem cell development to macrophages or granulocytes, we first determined that TREM‐2 was only expressed on fully differentiated macrophages. We further confirmed loss of TREM‐2 expression in macrophage colony forming receptor null mice, which cannot generate macrophages, thus demonstrating similar TREM‐2 expression patterns in human and mice. Studies of PU.1 restoration in PU.1 null cells demonstrated a requirement for PU.1 in TREM‐2 regulation. To determine the mechanisms for end‐stage myeloid lineage regulation, the human TREM‐2 promoter region was cloned, sequenced, and transcriptionally mapped and putative C/EBPalpha (cebpa) and pu.1 binding sites were identified. Functional studies showed requirements for both CEBPA and PU.1 for TREM‐2 activation. These findings define the mechanisms of lineage specific TREM‐2 regulation. We are now investigating the role of TREM‐2 in macrophage function during angiogenesis and inflammation.