Synovial Macrophages in Rheumatoid Arthritis: The Past, Present, and Future

Table 1

The functions of SMs in RA synovium.

Cell type	Mediator	Function
Polarization
SMs (M1)	TF and pathway: STAT1, IRF5, SOCS1, NF-κB pathway	Proinflammation; glycolysis; iron retention
	Cytokine: IL-1β, TNF-α, IL-12, IL-23
	Chemokine: CXCL9/10/11, CCL5
	Surface marker: MHCII
SMs (M2)	TF and pathway: STAT6, IRF4, SOCS3, KLF4, c-Myc	Anti-inflammation; oxidative phosphorylation; iron export
	Cytokine: IL-4, IL-10
	Chemokine: CCL17/22
	Surface marker:CD206, CD163,MGL
Cell-cell communications
Synovial fibroblasts (SF)	IL-1β, TNF-α	SMs promote SF proliferation.
Osteoclasts	IL-1β, IL-6, TNF-α	SMs promote osteoclasts activation.
Monocytes	IL-1β, IL-8, TNF-α, CCL2	SMs recruit monocytes.
Neutrophils	IL-1β, IL-8, TNF-α, CCL2	SMs recruit neutrophils.
T cells (Th1 cells)	TNF-α, IL-12	SMs promote Th1 polarization.
T cells (Th17 cells)	IL-23	SMs promote Th17 polarization.
B cells	Immune complex and autoantibody	B cells activate SMs.