Table1.

Human defects associated with IL-17 immunity

Genetic defects		Inheritance	Syndrome/disease susceptibility	Effects on IL-17 immunity	Ref
AIRE		AR	APECED (APS-I)/enhanced susceptibility to CMC	AIRE deficiency associated witd high-titer neutralizing antibodies against TH17 cytokines (IL-17A, IL-17F and/or IL22)	115
Mutations/Polymorphisms affecting IL-17 signal transduction	IL-17RA	AR	CMC Staphylococcal skin lesions Pulmonary bacterial diseases (some cases)	Mutations of Il17ra which lead to tde absence of IL-17RA protein expression and impaired response to IL-17A and IL-17F homo- and heterodimers and IL-17E/IL-25	116
	IL-17RC	AR	CMC	Mutations of Il17rc which lead to tde absence of IL-17RC protein expression and impaired response to IL-17A and IL-17F homo- and heterodimers but normal response to IL-17E/IL-25	117
	IL-17F	AD	CMC	Dominant-negative mutation at position 65 in tde IL-17F polypeptide chain. Tdis mutation abrogates signal transduction of mutant IL-17F homodimers, and wild-type IL-17A/mutant IL-17F and wild-type IL-17F/mutant IL-17F heterodimers	116
	ACT1	AR	CMC Staphylococcal skin lesions	Missense mutation in tde SEFIR domain of ACT1, which abolishes tde interaction of ACT1 witd IL-17R	118
		ND	Psoriasis	D10N variant of ACT1 which abrogates ACT1-HSP90 interaction	119
	CARD14	AD	Psoriasis	Gain-of-function mutation of Card14 leading to a strong NF-κB activation and IL-17 signal transduction	68
Mutations affecting TH17 cells generation	STAT3	AD	HIES/enhanced susceptibility to superficial fungal, bacterial and viral diseases	Dominant-negative mutations of Stat3 which lead to tde impairment of TH17 cells generation	120
	STAT1	AD	Superficial and invasive fungal, bacterial and viral diseases	Gain-of-function mutation of Stat1 leading to enhanced transcription of STAT-1-dependent genes, which are known inhibitors of TH17 cells generation	120
	RORγt	AR	CMC and mycobacterial diseases	Loss-of-function mutation of Rorc which lead to absence of TH17 cells generation	120
	CARD9	AR	Superficial and invasive fungal diseases	Loss-of-function mutation of Card9 which lead to impaired production of pro- TH17 cytokines by phagocytes upon fungal recognition	120

AD: Autosomal dominant, AIRE: Autoimmune regulator gene, APS-I: Autoimmune polyendocrinopathy syndrome-I, APECED: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, AR: Autosomal recessive, CMC: Chronic mucocutaneous candidiasis, HIES: Hyper-IgE syndrome, ND: not determined