The Essential Role of FoxO1 in the Regulation of Macrophage Function

Table 1

Implications of FoxO1 in macrophage functional regulation under disease settings.

Manipulation	Upstream of FoxO1	FoxO1 activity	Effect on macrophage	Disease phenotype	Reference
Chemical compounds
AS1842856	—	Inhibited	M2↓	Asthma↓	[36]
Ang- [1–7]	TLR4–JNK	Inhibited	M1↓	Inflammation ↓	[47]
AA	JNK	Inhibited	Proliferation↓	—	[48]
ATRA	RARα	Inhibited	M2↑	Liver ischemia -reperfusion injury↓	[49]
ICG-001	β-Catenin	Enhanced	MMT↓	Kidney fibrosis↓	[21]
Genetic (indirect)
Nrf2 cKO	Nrf2–Akt	Inhibited	M1↑	Liver ischemia -reperfusion injury↑	[50]
CypD cKO	—	Inhibited	M1↓	Inflammation ↓	[37]
LysM-Irs2	Akt		M2↓	Obesity↑	[18]
LysM-Sirt6	—	Enhanced	M1↑	Rheumatoid arthritis↑	[20]
LysM-PTEN	—	Inhibited	M1↓	Acute lung injury ↓	[43]
PTEN siRNA	Akt/β-catenin	Inhibited	M1↓	Liver ischemia -reperfusion injury↓	[51]
CaMKKβ siRNA	—	Enhanced	Autophagy↑	Anti-bacteria↑	[22]
LKB1 vector	—	Enhanced	M1↑	Tuberculosis infection↓	[16]
ADAR1 adenovirus	miR-21	Enhanced	M2↑	Allogeneic graft rejection↓	[34]
Genetic (direct)
LysM-FoxO1	—	Inhibited	M2↑; M1↓	S. aureus infection↑	[23]
LysM-FoxO1	HIF-1α	Inhibited	M2↑	Tumor↑	[32]
FoxO1 cKO	TLR4-PI3K-Akt	Inhibited	M1↓	Obesity↓	[17]
FoxO1 shRNA	Insulin–Akt	Inhibited	Apoptosis↓	Obesity↓	[1]

Abbreviations: AS1842856, a pharmacologic inhibition of FoxO1; Ang, angiotensin; AA, arachidonic acid; ATRA, all-trans retinoic acid; RARα, retinoic acid receptor α; ICG-001,a known inhibitor of β-catenin/TCF transcription by selectively blocking the β-catenin/CREB-binding protein interaction; MMT, macrophage–myofibroblast transition; Nrf2, nuclear factor erythroid 2-related factor 2; CypD, cyclophilin D; PTEN, phosphatase and tensin homologue; LKB1, liver kinase B1; ADAR1, adenosine deaminase acting on double-stranded RNA 1.