Table 1.

The main experimental evidence and findings about macrophge autophagy in organ fibrosis obtained in vitro and in vivo.

Treatment	Models	Macrophage autophagy	Type of macrophage	Outcome	In vitro or in vivo	References
CS	–	AM autophagy↑	AMs	CS-induced PF↓	In vivo	(79)
Trehalose	–	AM autophagy↑	AMs	CS-induced PF↓	In vivo and in vitro	(80, 81)
Dioscin	–	AM autophagy↑	AMs	CS-induced PF↓	In vivo	(79, 82)
Dioscin	(Atg5flox/floxDppa3-Cre/+) mice	AM autophagy↓	AMs	CS-induced PF↑	In vivo	(79)
MicroRNA-205-5p	–	AM autophagy↑	AMs	CS-induced PF↓	In vivo and in vitro	(83)
CS	(Atg5fl/flLysM-Cre+) mice	Monocyte-derived macrophage autophagy↓	Monocyte-derived macrophages	CS-induced PF↑	In vivo	(84)
SARS-CoV-2-	–	–	CD163+ monocyte-derived macrophages↑	SARS-CoV-2-induced PF↑	Patients	(85)
Viral and bacterial	Deficiency of TRIM29	Unknown	AMs↓	Type I interferons↑, less susceptible to the influenza virus	In vivo	(87)
Macrophage depletion	I/R	–	Macrophages↓	Renal fibrosis↓	In vivo	(95, 96)
High-fat diet feeding and treated with low-dose lipopolysaccharide	(Atg5fl/flLysM-Cre+) mice	Macrophage autophagy↓	proinflammatory M1↑, anti-inflammatory M2↓	Inflammation↑	In vivo	(21)
USP19	–	Macrophage autophagy↑	Anti-inflammatory M2↑	Inflammation↓	In vivo	(24)
–	UUO mouse model	Macrophage mitophagy↑	Macrophage M1 polarization↓	Inflammation, renal fibrosis↓	In vivo	(100)
Rapamycin	–	Macrophage autophagy↑	Macrophage M1 polarization↓	Renal fibrosis↓	In vivo and in vitro	(102)
Quercetin	Obstructive mouse model	–	Macrophage M1 polarization↓	Renal fibrosis↓	In vivo	(103)
Repeated intraperitoneal injection of carbon tetrachloride	Specifically knock out the Atg5 in the myeloid lineage	Macrophage autophagy↓	–	Liver injury, chronic liver inflammation, and liver fibrosis↑	In vivo	(108)
Pharmacological and gene-level interventions to inhibit LAP	–	–	Controlling polarization of macrophages	liver inflammation, and liver fibrosis↑	In vivo	(113)
–	Myocardial infarction	–	CCR2+ macrophages	Cardiac fibrosis and heart failure	In vivo	(127)
Inhibition of TLR2	–	–	Macrophages↓	Ang II-induced cardiac fibrosis↓, inflammatory response↓	In vivo	(135)
Adiponectin	–	Macrophage autophagy↑	–	Ang II-induced cardiac fibrosis↓, inflammatory response↓	In vivo and in vitro	(136)

AM: alveolar macrophage; CS: crystalline silica; PF: pulmonary fibrosis; UUO: unilateral ureteral obstruction; I/R: ischemia/reperfusion; USP19: ubiquitin-specific protease 19; LAP: LC3-associated phagocytosis; CCR2-: C-C chemokine receptor type 2 negative; CCR2+: C-C chemokine receptor type 2 positive.

↑ means this biological process is activated.

↓ means this biological process is suppressed.