Table 2.

Studies implicating macrophage phenotype in non-biomaterial-mediated fibrosis

	Fibrosis Model	Species	Macrophage-associated Experimental Condition	Outcome	Reference
M1-associated studies	idopathic pulmonary fibrosis	human	-	↑ expression of IL1β, collagen type I and III, fibronectin	[99]
	cardiac fibrosis	murine	IL6 knockout	↓ expression of αSMA, TGFβ1, collagen	[112]
	bleomycin-induced fibrotic legions	murine	STAT3 knockout	↓ expression of SOCS3, IL10, and decorin. ↑ expression of TGFβ1	[115]
M2-associated studies	scenescent muscle	murine	-	↑ collagen, tissue stiffness, ↓ nNOS	[118]
	scenescent muscle	murine	muscle-specific nNOS transgene	↓ M2 macrophages and muscle fibrosis in older muscle tissue	[87]
	endometriosis	murine (Balb/C)	-	↓ M2 macrophages (CD163), ↑ collagen, αSMA, SMAD3, and CD41	[120]
	endometriosis	murine (C57BL/6)	macrophage ablation and adoptive transfer of M1, M2a, or M2c macrophages	adoptive transfer of M2a macrophages (MRC1) ⟹ ↑ collagen I, TGFβ1, αSMA compared to M1 (iNOS) or M2c (VTCN1)	[120]
	tissue fibrosis	murine	IL4Rα knockout	↓ M2 markers (CD163, MRC1, PDGFB, IL10) and unchanged M1 markers (IL1β, TNFα, IL) vs. controls. M2a-derived RELMα ⟹ ↑ LH2 in fibroblasts	[124]
	fibrotic chronic pancreatitis	murine and human	IL4Rα knockout, macrophage depletion, and IL4/IL13 blocking antibodies	IL4/IL13 blocking ⟹ ↓ M2a macrophages and decrease in fibrosis	[125]
	bleomycin-induced lung fibrosis	murine	IL13Rα2 blocking antibody	↓ TGFβ1 and collagen deposition	[126]
	heart-allograft fibrosis	murine	IL13Rα2 blocking via siRNA	fibrosis was prevented	[127]
	failing renal allograft	human	-	CD68, aSMA, MRC1	[129]
	renal fibrosis	murine	SMAD3 knockout	macrophage-myofibroblast transition	[130]