Table 2.

Studies of the protective roles of PPARγ in autoimmune diseases.

Autoimmune diseases	Cell types	Animal models	PPARγ agonists	Effects	Ref
Graves ophthalmopathy (GO)	Myoblasts from extraocular muscles (EOM)		pioglitazone	Diminish the expression of TNF-α-induced TGF-β, hyaluronan (HA), and HAS3	[62]
Autoimmune thyroid diseases	thyrocytes		Pioglitazone and RGZ	Inhibit the expression and secretion of the chemokines CXCL10 and CXCL11	[66,67]
Multiple sclerosis			thiazolidinedione pioglitazone, ziglitazone and nonthiazolidinedione PPAR-γ agonist GW347845	Reduce the T cell proliferation and production of the cytokines TNF- α and IFN- γ induced by phytohemagglutinin	[79]
Rheumatoid arthritis			Pioglitazone	Alleviate insulin resistance	[91]
Systemic sclerosis	myofibroblast		Both natural and synthetic agonists	Abrogate the TGF-beta-induced stimulation of collagen synthesis and myofibroblast differentiation.	[102]
		mouse model of bleomycin-induced scleroderma	15-deoxy-Delta (12,14)-prostaglandin J(2)	(1) Reduce dermal sclerosis, hydroxyproline content, and dermal thickness (2) Downregulate expression of transforming growth factor beta and connective tissue growth factor	[103]
		mouse model of bleomycin-induced scleroderma	Rosiglitazone	Attenuate inflammation, dermal fibrosis, and subcutaneous lipoatrophy	[104]
		mouse model of bleomycin-induced scleroderma	Ajulemic acid	(1) Prevent experimental bleomycin-induced dermal fibrosis and modestly reduce its progression (2) Counteract the progression of pulmonary fibrosis	[117,118]
		mouse model of bleomycin-induced scleroderma	triterpenoid CDDO	Attenuate TGF-β signaling and dermal fibrosis	[119]
		mouse model of bleomycin-induced scleroderma	Pan PPAR agonist IVA337	(1) Decrease extracellular matrix deposition and reduce expression of phosphorylated SMAD2/3-intracellular effector of TGF-β1 (2) Downregulate several markers of inflammation	[120]
		Mice bearing fibroblast-specific deletion of PPARγ		Fibroblast-specific deletion of PPARγ results in enhanced susceptibility to bleomycin-induced skin fibrosis	[105]
		Mice bearing adipocyte-specific deletion of PPARγ nuclear corepressor (NCoR)		Adipocyte-specific deletion of PPARγ nuclear corepressor (NCoR) showed protective effects on experimental skin fibrosis and inflammation.	[106]
		mouse model of bleomycin-induced scleroderma	EHP-101	Inhibit the expression of genes involved in the inflammation, vasculogenesis and fibrogenesis.	[116]
	SSc fibroblasts		rosiglitazone and pioglitazone	Reduce cell proliferation and cell viability and increase apoptosis	[108]
	ECV304 cells			Lack of PPARγ results in an angiogenic potential	[111]
		Mice with targeted deletion of PPARγ in SMCs		Spontaneously develop PAH	[112]
Systemic lupus erythematosus	human THP-1 and SLE patient-derived macrophages	MRL-lpr mice deficient in adiponectin	rosiglitazone and pioglitazone	(1) Increased PPARγ expression represses the CD40/CD40L signaling pathway (2) Induce transcriptional repression of various genes involved in T cell responses (3) Reduce the production of autoantibodies	[124,126,127]
	DCs derived from SLE monocytes		Rosiglitazone combined with dexamethasone	Induce stable autologous tolerogenic dendritic cells	[128]
	monocyte-derived macrophages from SLE patients		Pioglitazone	Induce the M2 phenotype of monocyte-derived macrophages from SLE patients	[130]
Sjogren Syndrome	SGEC			Inhibit activation of the NF-κB and IL-1β pathways and apoptosis induced by proinflammatory agents	[134]
	Cultured lacrimal gland acinar cells			Inhibit the IL-1β pathway	[135]
		nonobese diabetic mice with Sjogren's syndrome	Rosiglitazone	Ameliorates histopathologic changes in the salivary glands through the reduction in Th1 cytokines	[136]
Primary biliary cirrhosis		MRL/lpr mice with a PBC-like cholangitis	prostaglandin D metabolite 15-deoxy-Δ (12,14)-prostaglandin J2 (15d-PGJ2)	Reduce portal inflammation and T cell numbers in portal tracts	[140]