Table 1.

Targeting chemokine pathways in animal models of PF and human PF.

Target	Model	Species	Inhibition or Genetic Knockout	Outcome	Notes	Refs.
CCL1	BLM-induced PF	Mouse	CCL1 mAb	Effective	Reversed the profibrotic phenotype of fibroblasts; reduced lung collagen deposition; improved lung function; decreased hydroxyproline levels	[20]
	hMSC-induced PF	Mouse	CCL1 mAb	Effective	Suppressed immune cell infiltration; improved lung injury	[19]
CCL2	BLM-induced PF	Mouse	CCL2 deficiency	Effective	Alleviated lung fibrosis; reduced mononuclear phagocyte recruitment; decreased collagen deposition and CTGF expression	[28,29,30]
	IPF	Human	CCL2 mAb (Carlumab)	Not effective	No benefit in lung function	[45]
CCR2	BLM-induced PF; FITC-induced PF	Mouse	CCR2 deficiency	Effective	Decreased collagen deposition; attenuated hydroxyproline content; reduced profibrotic cytokines production	[28,29,30]
CCL3	BLM-induced PF	Mouse	CCL3 mAb	Effective	Reduced pulmonary mononuclear phagocyte accumulation and fibrosis	[50,51,52]
	BLM-induced PF	Mouse	CCL3-binding protein (evasin-1)	Effective	Attenuated pulmonary leukocytes and fibrosis; decreased profibrotic cytokines production
	BLM-induced PF	Mouse	CCL3 deficiency	Effective	Reduced collagen accumulation; attenuated profibrotic cytokine production
CCR4	BLM-induced PF	Mouse	CCR4 deficiency	Effective	Decreased mortality; attenuated hydroxyproline contents	[73]
CCL21	i.v. adoptive transfer of either IPF/UIP or NSIP primary fibroblast lines to C.B-17SCID/bg mice	Mouse	CCL21 mAb	Effective	Decreased hydroxyproline levels; attenuated lung interstitial remodeling	[99]
CCR7	i.v. adoptive transfer of either IPF/UIP or NSIP primary fibroblast lines to C.B-17SCID/bg mice	Mouse	CCR7 mAb	Effective	Decreased hydroxyproline levels; attenuated lung interstitial remodeling; reduced whole-lung levels of CCL21	[99]
CCL24	BLM-induced PF	Mouse	CCL24 mAb (CM-101)	Effective	Reduced collagen deposition and fibrosis; attenuated immune cell infiltration	[104]

hMSC: human mesenchymal stem cell; i.v.: intravenous; IPF/UIP: idiopathic pulmonary fibrosis/usual interstitial pneumonia; NSIP: nonspecific interstitial pneumonia; C. B-17SCID/bg mice: C. B-17 severe combined immunodeficiency (SCID)/beige (bg) mice; CTGF: connective tissue growth factor.