CX 3 CR 1 + CD 115 + CD 135 + common macrophage / DC precursors and the role of CX 3 CR 1 in their response to infl

The Rockefeller University Press $30.00 J. Exp. Med. Vol. 206 No. 3 595-606 www.jem.org/cgi/doi/10.1084/jem.20081385 595 Monocytes, macrophages, and DCs form networks of phagocytic cells throughout most tissues, the development of which are dependent on the CSF-1 receptor (csf1r, also known as CD115, c-fms, and M-CSF receptor) ( 1, 2 ). These cells, which are sometimes referred to as the mononuclear phagocyte system, play major roles in development, scavenging, infl ammation, and antipathogen defenses ( 3, 4 ). They are highly heterogeneous in phenotype, tissue distribution, and function ( 3, 5, 6 ). Considerable attention is currently focused on the characterization of their progenitors and precursors, the signals driving their development in the BM, their migration to tissues, and their homeostasis in peripheral tissues. CSF-1R and its two known ligands, M-CSF and IL34 ( 7 ), are critical for the development of this lineage because M-CSF – defi cient mice (op/ op and csf1 / ) have a milder phenotype than the Csf1r-defi cient mice ( 8 ). Other cytokines, such as GM-CSF, FLT3, LT1 2 (LT ) ( 9 – 15 ), and chemokines ( 16, 17 ) have also been shown to control the development and homeostasis of the macrophage and DC networks. Cellular cloning and transplantation studies have shown that many macrophage subsets, most of the conventional DCs (cDCs) in the secondary lymphoid organs of mice, and at least a fraction of the DCs in the mouse thymus probably originate from myeloid progenitors ( 18 – 20 ). CORRESPONDENCE Frederic Geissmann: [email protected]