Figure 1.

Monocyte development and mobilization. In the bone marrow (BM), pro-inflammatory Ly6C⁺ monocytes are derived from cMoPs that are differentiated from a series of hematopoietic stem cells (HSCs) by transcription factors PU.1, interferon regulatory factor 8 (IRF8), and Kruppel-like factor 4 (KLF4). Ly6C⁺ monocytes emigrate out of the BM in a C-C chemokine receptor 2 (CCR2)-dependent manner, and the ligands of CCR2, C-C motif ligand 2 (CCL2) and C-C motif ligand 7 (CCL7), stimulate Ly6C⁺ monocyte mobilization into the blood. The development of anti-inflammatory Ly6C⁻ monocytes from Ly6C⁺ monocytes depends on CCAAT enhancer–binding protein β (C/EBPβ)–dependent nuclear receptor subfamily 4 group A member 1 (NR4A1). Ly6C⁻ monocytes crawling on the endothelium in the periphery act in an immune surveillance capacity to maintain homeostasis.