Table 2.

AHR ligands linkage with human autoimmune diseases and animal models related with Th17 development

AHR ligand	Ligand type	Sources of ligand	Cell type/animal model used	Observed effect	Relevant diseases	Biological relevance in the pathology of disease
TCDD	Agonist	Combustion products, forest fire, cigarette smoke	Fibroblast-like synoviocyte cell line (MH7A)	Enhanced IL-1 mRNA	Rheumatoid arthritis	Aggravate [112]
			RA patient-derived synoviocites	Upregulated IL-1β, IL-6 and IL-8 production	Rheumatoid arthritis and osteoarthritis	Aggravate [105]
			2,4,6-trinitrobenzenesulfonic acid (TNBS) murine model of colitis	Decreased IL-6 and induced FoxP3+ Tregs	Inflammatory bowel disease	Suppress [164]
			C57BL/6 mice	Induced expansion of CD4+ CD25+ Foxp3+ Treg population	Experimental autoimmune encephalomyelitis	Suppress [95]
B[a]P	Agonist	Wood burning, exhaust fumes (especially diesel engine), charbroiled food, cigarette smoke	Fibroblast-like synoviocyte cell line (MH7A)	Enhanced IL-1 expression	Rheumatoid arthritis	Aggravate [112]
			Human monocyte-derived DCs	Reduced IL-6 production	Rheumatoid arthritis	Contribute to pathogenesis [165]
3-MC	Agonist	Combustion products	Fibroblast-like synoviocyte cell line (mh7a)	Enhanced IL-1 expression	Rheumatoid arthritis	Aggravate [112]
ITE	Agonist	Originally isolated from porcine lung	Murine T cells from thymus and mesenteric lymph nodes	Induced FoxP3+ Treg cells	Collagen-induced arthritis	Suppress [121]
			PBMCs from AR patients	Inhibited Th17 differentiation and production of IL-17 and IL-22	Allergic rhinitis	Suppress [107]
			DCs and CD4+ T cells from AR patients	Inhibited IL-1β and IL-6, induced IL-10 secretion by DCs, inhibited IL-17 and induced IL-10 expression and by CD4+ T cells and Th17 cell expansion in vitro	Allergic rhinitis	Suppress [123]
			monocyte-derived DCs and CD4+ T cells from BD patients	Inhibited production of IL-1β, IL-6, IL-23, TNFα and induced IL-10 by DCs and inhibited Th17 response	Behcet’s disease	Suppress [122]
FICZ	Agonist	Tryptophan photoproduct	CD4+ T cells from B6 mice and human	Increased expression of Il17a, Il17f and Il22	Experimental autoimmune encephalomyelitis	Aggravate [94]
			Lamina propria mononuclear cell from IBD patients and TNBS murine model of colitis	Upregulated production of IL-22	Inflammatory bowel disease	Suppress [167]
KYNA	Agonist	Generated from tryptophan by enzymatic process via kynurenine pathway	CD4+ T cells from BALB/c mice	Increased production of IL-17	Autoimmune gastritis	Aggravate [132]
I3S	Agonist	Originate from a tryptophan metabolite indole by intestinal bacteria	T cells from BALB/c mice	Increased phosphorylation of STAT3 and stimulated expression of RORγt, and in vitro Th17 differentiation	Collagen-induced arthritis	Aggravate [136]
I3C	Agonists	Generated from tryptophan from cruciferous vegetables (broccoli, brussel sprouts, cabbage, cauliflower, collard greens, sprouts, kale)	T cells from C57BL/6 mice	Increased number of Tregs and reduced number of Th17 cells	Experimental autoimmune encephalomyelitis	Suppress [138]
DIM
RES	Antagonist/agonist	Polyphenolic phytoalexin from red grape, red wine, cacao, peanut, mulberries, and pines	Lymphocytes from DBA1 mice	Inhibited production of IL-6, IL-17 and Th17 cell differentiation	Collagen induced arthritis	Suppress [166]
			Splenic and brain derived mononuclear cells and macrophages from SJL/J mice	Induced number of IL-17+ IL-10+ T cells and increased IL-12/23 p19 and p35 production by macrophages, decreased expression of IL-6 and IL-12/23p40 expression by macrophages	Experimental autoimmune encephalomyelitis	Suppress [151]
			C57BL/6 mice and mouse T lymphoma cell line (EL4)	Increased expression of FoxP3	Experimental allergic encephalomyelitis	Suppress [150]
Baicalin	Agonist	Flavone type flavonoid in the genus Scutellaria (e.g., Blue skullcap)	CD4+ T cells from C57BL/6 (B6) and lupus-prone MRL/lpr mice	Inhibited in vitro and in vivo differentiation of Th17, inhibited expression of CCR6, IL-6 receptor and RORγt, upregulated expression of Foxp3 and down-regulated RORγt-mediated IL-17	Lupus nephritis	Suppress [158]
α-NF	Antagonist	Flavone type flavonoid	Fibroblast-like synoviocyte cell line (MH7A)	Suppressed IL-1 expression via inhibition of B[a]P and 3-MC	Rheumatoid arthritis	Suppress [112]