The regulation of inflammation by interferons and their STATs

Figures & data

Table 1. Regulation of chemokine synthesis by IFN and STATs 1/2

Cell/animal	Stimulus/disease	IFN type involved	STAT involved	Chemokine regulated	References
Mouse macrophages	IFN-γ or IFN-γ/TNF	IFN-γ	STAT1	CCL2/MCP1 ↑	37, 45 and 128
				CXCL9/MIG ↑
				CXCL10/IP10 ↑
				CCL12/MCP5 ↑
	IFN-γ/PamCys	IFN-γ	nd	CCL2/MCP1 ↑	52
	LPS	nd	STAT1	CXCL10/IP10 ↑	45 and 129
				CCL12/MCP5 ↑
	LPS/IFN-γ	IFN-γ	STAT1	CXCL1/KC/GROα ↓	45
				CXCL2/MIP2/GROβ ↓
				CCL2/MCP1 ↓
				CCL4/MIP1β ↓
	TNF	IFN-β	STAT1	CCL5/RANTES ↑	11
				CXCL9/MIG ↑
				CXCL10/IP10 ↑
	Listeria monocytogenes	IFN-I	nd	CCL2/MCP1 ↑	42
Mouse splenocytes	IFN-α	IFN-α	STAT1	CCL2/MCP1 ↓	46
				CCL5/RANTES ↓
				CCL7/MCP3 ↓
Human monocytes	IFN-γ	IFN-γ	STAT1	Inhibition of migration in response to CCL2	130
	TNF	IFN-β	STAT1	CCL5/RANTES ↑	11
				CXCL9/MIG ↑
				CXCL10/IP10 ↑
	M1 polarization (IFN-γ/LPS)	IFN-γ	nd	CCL5/RANTES ↑	44 and 131
				CCL15/MIP1δ ↑
				CCL20/MIP3α ↑
				CXCL9/MIG ↑
				CXCL10/IP10 ↑
Human monocyte-derived DC	Sendai virus	IFN-I	ISGF3	CCL19/MIP3β ↑	40
	Salmonella Typhimurium
Human PBMC	IFN-λ	IFN-λ	nd	CXCL9/MIG ↑	132
				CXCL10/IP10 ↑
				CXCL11/I-TAC ↑
Mouse primary cortical neurons	IFN-α	IFN-α	STAT1	CXCL10/IP10 ↑	133
Human astrocytes	IFN-γ/IL-1β	IFN-γ	nd	CXCL11/I-TAC ↑	36
	IFN-β/IL-1β	IFN-β	ISGF3 (?)	CCL5/RANTES ↑	32
Mouse microglia	IFN-γ	IFN-γ	STAT1	CXCL9/MIG ↑	41
Human plasmacytoid DC (MS patient)	IFN-β/TLR9 ligand	IFN-β	nd	CCL3/MIP1α ↓	48
				CCL4/MIP1β ↓
				CCL5/RANTES ↓
Human T cells (MS patient)	IFN-β	IFN-β	nd	CCL3/MIP1α ↓	47
				CCL5/RANTES ↓
				CCR5 ↓
Mouse	MCMV infection	IFN-I	nd	CCL2/MCP1 ↑	49
				CCL3/MIP1α ↑	50
				CCL7/MCP3 ↑	51
				CCL12 ↑
Mouse liver	MCMV infection	IFN-γ	nd	CXCL9/MIG ↑	49
Mouse brain	LCMV infection	IFN-γ	nd	CCL2/MCP1 ↑	55
				CCL3/MIP1α ↑
				CCL5/RANTES ↑
				CXCL10/IP10 ↑
Mouse cornea	HSV-1	IFN-α	nd	CCL2/MCP1 ↑	34
Mouse	Vaccinia virus	IFN-I, IFN-γ	nd	CXCL9/MIG ↑	134
	West Nile virus	IFN-I	nd	CCL2/MCP1 ↑	135
				CCL5/RANTES ↑
				CXCL10/IP10 ↑
	Influenza virus	IFN-I	nd	CXCL1/KC ↓	23
	Streptococcus pneumoniae			CXCL2/MIP2 ↓
Mouse peritoneal cavity	Listeria monocytogenes	IFN-I	nd	CCL2/MCP1 ↑	42
		nd	STAT1 (macrophages)	CCL3/MIP1α ↓	26
			STAT1 (DC)	CCL2/MCP1 ↑
				CCL5/RANTES ↑
			STAT1 (T cells)	CCL2/MCP1 ↑
				CCL5/RANTES ↑
Mouse	Francisella tularensis	IFN-γ	nd	CCL2/MCP1 ↑	52
	Polymicrobial peritonitis (CASP)	IFN-I	nd	CCL2 ↓	78
	Polymicrobial peritonitis (CLP)	IFN-I	nd	CXCL10 ↑	53
	Trypanosoma cruzi	IFN-γ	nd	CXCL9/MIG ↑	136
				CXCL10/IP10 ↑
	Paracoccidioides brasiliensis	IFN-γ	nd	CCL5/RANTES ↑	137
				CXCL1/KC/GROα ↓
				CCL3/MIP1α ↓
	Candida albicans	IFN-I	nd	CCL2/MCP1 ↑	71
				CXCL1/KC/GROα ↑
Mouse thyroid gland	IFN-γ transgene (thyroid gland)	IFN-γ	nd	CXCL9/MIG ↑	56
				CXCL10/IP10 ↑
				CCL4/MIP1β ↑
				CCL5/RANTES ↑
				CXCL11/I-TAC ↑
Mouse mast cells	Imiquimod	IFN-I	nd	CCL2/MCP1 ↑	59
Mouse	TNF	IFN-I	nd	CXCL9/MIG ↑	27
				CXCL10/IP10 ↑
				CXCL11/I-TAC ↑
	Allergic asthma	IFN-γ	STAT1	CXCL9/MIG ↑	58
				CXCL10/IP10 ↑
	ConA-induced hepatitis	IFN-γ	STAT1	CXCL5/ENA-78 ↑	138
				CXCL9/MIG ↑
				CXCL10/IP10 ↑
				CXCL11/I-TAC ↑
Mouse (astrocytes)	EAE	IFN-γ	nd	CXCL10/IP10 ↑	57
Human (MS patient)	IFN-β	IFN-β	nd	CCL2/MCP1 ↑	139
				CXCL10/IP10 ↑

nd, not determined

Figure 1. The control of Inflammation by interferons and their STATs. Arrows indicate whether a particular event is increased by IFN, decreased or whether either can occur in different inflammatory diseases. The IFN-γ receptor operates by activating a STAT1 dimer, whereas both the type I IFN (IFN-α/β) and IFN-λ receptors operate through the ISGF3 (STAT1/STAT2/IRF9) complex.

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