International Journal of Inflammation

Review Article

Th17 Response and Inflammatory Autoimmune Diseases

Table 1

Preclinical mouse models showing a role for Th17 cells and the IL-17 pathway in autoimmunity.


Disease	Model	Role of Th17	Reference

Rheumatoid arthritis	Collagen-induced arthritis (CIA)	IL-23 (p19 subunit) KO mice have less Th17 cells and reduced disease severity	[35]
	Collagen-induced arthritis (CIA)	IL-17A KO mice have reduced disease incidence and severity	[36]
	IL-6R subunit gp130 (Y759F) mutation	Enforced IL-6 expression enhances disease progression in an IL-17A-dependent manner	[37]
	SKG-dominant active ZAP70 mutant	IL-17A KO mice are resistant to arthritis	[39]
	HTLV-I Tg mice	IL-17A KO mice are resistant to arthritis	[41]

Inflammatory Bowel disease	Adoptive transfer of CD4⁺CD45RB^hi cells to lymphopenic mice	IL-17A KO CD4⁺ T cells accelerated T-cell-mediated intestinal damage	[42]
	Adoptive transfer of CD4⁺CD45RB^hi cells to lymphopenic mice	IL-17A, IL-17F, or IL-22 KO T-cells-induced colitis equally compared to WT	[43]
	Dextran sodium sulfate (DSS)	IL-17F KO or IL-17A KO or mice treated with an anti-IL-17A antibody showed severe weight loss and colonic epithelial damage	[44, 45]
	Dextran sodium sulfate (DSS)	IL-17A KO showed substantially reduced colitis based on both clinical score and mortality	[46]

	Topical application of imiquimod (IMQ)	Dermatitis is blocked in IL-23R KO and IL-17R KO mice	[53]
Psoriasis	IL-23 injection	IL-6-dependent accumulation of Th17 cells in psoriatic skin, dermatitis was greatly reduced in IL-22 KO or IL-17A KO mice	[55, 56]
	K5.Stat3C transgenic mice	Constitutively express activated Stat3 within keratinocytes promotes Th17 cells, and anti-IL-23 was shown to block epidermal hyperplasia; however, anti-IL-17 had only partial effect	[57]

Type 1 diabetes	RIP-OVA mice (mice expressing OVA peptide in pancreatic beta islet cells )	IL-17 producing CD8⁺ T cells (Tc17) cause diabetes in an IL-17A- and IL-17F-dependent manner when adoptively transferred to RIP-OVA mice	[59]
Type 1 diabetes	Nonobese diabetes (NOD)	Anti-IL-17A antibodies inhibit diabetes during the effector phase of disease (at 10 weeks of age) but not during the initiation of disease (mice less than 5 weeks of age)	[60]