Human IL-23 is essential for IFN-γ-dependent immunity to mycobacteria.
Fiche publication
Date publication
février 2023
Journal
Science immunology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak, Dr CARAPITO Raphaël
Tous les auteurs :
Philippot Q, Ogishi M, Bohlen J, Puchan J, Arias AA, Nguyen T, Martin-Fernandez M, Conil C, Rinchai D, Momenilandi M, Mahdaviani SA, Keramatipour M, Rosain J, Yang R, Khan T, Neehus AL, Materna M, Han JE, Peel J, Mele F, Weisshaar M, Jovic S, Bastard P, Lévy R, Le Voyer T, Zhang P, Maglorius Renkilaraj MRL, Arango-Franco CA, Pelham S, Seeleuthner Y, Pochon M, Ata MMA, Al Ali F, Migaud M, Soudée C, Kochetkov T, Molitor A, Carapito R, Bahram S, Boisson B, Fieschi C, Mansouri D, Marr N, Okada S, Shahrooei M, Parvaneh N, Chavoshzadeh Z, Cobat A, Bogunovic D, Abel L, Tangye SG, Ma CS, Béziat V, Sallusto F, Boisson-Dupuis S, Bustamante J, Casanova JL, Puel A
Lien Pubmed
Résumé
Patients with autosomal recessive (AR) IL-12p40 or IL-12Rβ1 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 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 -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 in a single lymphocyte subset but is required for IFN-γ-dependent immunity to in at least two lymphocyte subsets.
Référence
Sci Immunol. 2023 02 17;8(80):eabq5204