Regulation of myeloid cell population kinetics and phenotype by CSF-1 and GM-CSF (#293)
GM-CSF (CSF-2) and CSF-1 are key cytokines for the mononuclear phagocytes, including monocytes, macrophages and dendritic cells (DCs). GM-CSF is critical for in vitro monocyte-derived DCs (Mo-DCs) generation and the development of resident CD103+ DCs in some tissues. In contrast, CSF-1 is essential for the homeostasis of monocyte/macrophage lineage cells. However, clear delineation of DC subsets, Mo-DCs and classical DCs (cDCs), has remained relatively unclear because of many overlapping features of these cells such as surface markers, making it difficult to discern the differential roles of GM-CSF or CSF-1 in controlling such cells.
In this study, we assess the effects of GM-CSF and CSF-1 on myeloid-lineage populations during inflammation utilizing a number of animal models. Peritoneal exudate cells (PECs) were taken from antigen (mBSA)-induced peritonitis (AIP) or thioglycolate-induced peritonitis. Spleen cells from intravenous LPS-challenged mice were examined. Mice also received anti-GM-CSF (22E9), anti-M-CSFR (AFS98), or control mAbs. Monocytes, macrophages, and DC subsets (Mo-DCs and cDCs) were monitored by flow cytometry.
We classified all monocyte descendants, including monocytes, monocyte-derived macrophages and Mo-DCs, by their CSF-1 receptor/CD115 expression, setting them apart from cDC lineage. Inflammatory Mo-DCs were found in the AIP PECs, but not in thioglycolate-PECs or LPS-challenged spleens, and were depleted specifically in GM-CSF-/- or anti-GM-CSF-treated mice. AIP Mo-DCs, macrophages, and monocytes were all depleted following CSF-1R neutralization. In contrast, cDCs subsets in all tissues examined were relatively unaffected by the GM-CSF or CSF-1R neutralization. In summary, GM-CSF deletion or anti-GM-CSF treatment abrogated the accumulation of inflammatory Mo-DCs, with no effect on nonlymphoid tissue cDCs, in T cell-dependent inflammation; in contrast, the CSF-1 receptor was important for all inflammatory monocyte descendants, but not the cDC lineage populations.