Human IL-23 is essential for IFN-γ-dependent immunity to mycobacteria.
Sci Immunol
; 8(80): eabq5204, 2023 02 17.
Article
em En
| MEDLINE
| ID: mdl-36763636
ABSTRACT
Patients with autosomal recessive (AR) IL-12p40 or IL-12Rß1 deficiency display Mendelian susceptibility to mycobacterial disease (MSMD) due to impaired IFN-γ production and, less commonly, chronic mucocutaneous candidiasis (CMC) due to impaired IL-17A/F production. We report six patients from four kindreds with AR IL-23R deficiency. These patients are homozygous for one of four different loss-of-function IL23R variants. All six patients have a history of MSMD, but only two suffered from CMC. We show that IL-23 induces IL-17A only in MAIT cells, possibly contributing to the incomplete penetrance of CMC in patients unresponsive to IL-23. By contrast, IL-23 is required for both baseline and Mycobacterium-inducible IFN-γ immunity in both Vδ2+ γδ T and MAIT cells, probably contributing to the higher penetrance of MSMD in these patients. Human IL-23 appears to contribute to IL-17A/F-dependent immunity to Candida in a single lymphocyte subset but is required for IFN-γ-dependent immunity to Mycobacterium in at least two lymphocyte subsets.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interferon gama
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Interleucina-23
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Mycobacterium
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Infecções por Mycobacterium
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article