Table 1.
Diseases characterised by mutations and deficiencies in the IL-23/IL-17 pathway
| Disease | Genes/proteins involved | Common infections | Effect on IL-23/IL-17 signalling | References |
| MSMD | IL-12Rβ1 | Mycobacterium tuberculosis, salmonella, candida albicans |
Impaired IFN-γ-mediated immunity Decreased IL-17A-producing T cells Impaired IL-12 signalling |
176 181 183–187 189 |
| IL-12β | Mycobacterium tuberculosis, salmonella |
|||
| IFN-γR1 | Mycobacterium tuberculosis, salmonella, candida albicans |
|||
| STAT1 | Mycobacterium, candida albicans | |||
| IL-12/23 p40 | Mycobacterium tuberculosis, salmonella |
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| Salmonella infection | IL-23R | Salmonella | Th17 depletion, reduced production of IL-17A | 188 190 |
| IL-12/23p40 | ||||
| IL-12Rβ1 | ||||
| CMCD | STAT1 | Candida albicans, mycobacterium | Reduced production of IL-17A, IL-17F, IL-22 No response to IL-17A; reduced response to IL-17F; IL-17E response maintained Impaired neutrophil function |
182 183 191 193 202 |
| CARD9 | Candida albicans | |||
| IL-17RA | Candida albicans Staphylococcus |
|||
| IL-17RC | Candida albicans | |||
| IL-17F | Candida albicans | |||
| ACT1 | Candida albicans Staphylococcus |
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| APECED | AIRE | Candida albicans | Increased autoantibodies to IL-17A, IL-17F, and IL-22 | 194 197 |
| HIES | STAT3 | Candida albicans, staphylococcus, aspergillus | Increased serum IgE Eosinophilia Impaired development of Th17 cells Reduced IL-17A production |
49 198 201 203 |
| DOCK8 | Candida albicans, staphylococcus, aspergillus | |||
| TYK2 | Staphylococcus, mycobacterium, salmonella |
The genes and proteins involved and the resultant effects on IL-17 signalling that lead to increased susceptibility to certain infections are listed.49 176–201 IL-12 and IL-23 share cytokine and receptor subunits and the association with mycobacterial disease is thought to represent an effect on dysregulated IFN gamma production in the IL-12 pathway. Therefore IL-17 blockers or IL-23 p19 subunit blockers are not expected to have a link with mendelian susceptibility to mycobacterial disease.
AIRE, autoimmune regulator; APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; CARD9, caspase recruitment domain-containing protein 9; CMCD, chronic mucocutaneous candidiasis disease; DOCK8, dedicator of cytokinesis 8; HIES, hyper IgE syndrome; IFN, interferon; IFN-γR1, interferon gamma receptor 1; IL-12Rβ1, interleukin 12 receptor β1; MSMD, Mendelian susceptibility to mycobacterial disease; STAT, signal transducer and activator of transcription; TYK2, tyrosine kinase 2; Th-17, T helper 17 cell.