CD137 Induces Proliferation of Murine Hematopoietic Progenitor Cells and Differentiation to Macrophages

Abstract

CD137 is a member of the TNFR family, and reverse signaling through the CD137 ligand, which is expressed as a cell surface transmembrane protein, costimulates or activates APCs. CD137 and CD137 ligand are expressed on small subsets of bone marrow cells. Activation of bone marrow cells through CD137 ligand induces proliferation, colony formation and an increase in cell numbers. Compared with total bone marrow cells, the small subpopulation of progenitor cells that express no lineage markers but express CD117 cells (or Lin−, CD117+ cells) responds with the same activities to CD137 ligand signaling, but at a significantly enhanced rate. Concomitantly to proliferation, the cells differentiate to CFU granulocyte-macrophage and CFU macrophage, and then to monocytes and macrophages but not to granulocytes or dendritic cells. Hematopoietic progenitor cells differentiated in the presence of CD137 protein display enhanced phagocytic activity, secrete high levels of IL-10 but little IL-12 in response to LPS, and are incapable of stimulating T cell proliferation. These data demonstrate that reverse CD137 ligand signaling takes place in hematopoietic progenitor cells, in which it induces proliferation, an increase in cell numbers, colony formation, and differentiation toward monocytes and macrophages.

Involvement of CD137 Ligand Signaling in Neural Stem Cell Death

“…1B). However, the treatment of cells with soluble CD137-Fc had no effect on cell viability and cellular adherence to the culture dishes (data not shown), as previously reported in immune cells (Jiang et al, 2008).…”

“…It has previously been reported that CD137 is expressed in a wide range of cell types including monocytes (Langstein et al, 1998), epithelial cells (Schwarz et al, 1995) and hematopoietic stem cells (Jiang et al, 2008). Recently, several reports have also shown that brain cells constitutively express CD137 and its ligand (Reali et al, 2003;Yeo et al, 2012).…”

CD137 ligand mediates opposite effects in human and mouse NK cells and impairs NK-cell reactivity against human acute myeloid leukemia cells

“…15 Two recent studies demonstrated that CD137L is expressed on hematopoietic stem/progenitor cells in mice. 38, 39 Lee and coworkers reported that CD137L regulates myelopoiesis and inhibits differentiation of mouse hematopoietic progenitor cells. 38 is tempting to speculate on a potential role of CD137L in blocking differentiation of AML blasts and thus AML pathogenesis.…”

CD137 ligand‐mediated reverse signals increase cell viability and cytokine expression in murine myeloid cells: Involvement of mTOR/p70S6 kinase and Akt

“…Lee et al, reported that CD137L reverse signals inhibit myelopoiesis and the development of DC [33]. On the other hand, others showed that CD137L ligation enhances proliferation of hematopietic progenitor cells and its differentiation to monocytes, macrophages [34,35]. Reverse signals of CD137L enhances DC maturation and subsequent antigen-specific T-cell differentiation [36].…”