Human Il-23 Is Essential for Ifn-Γ–Dependent Immunity to Mycobacteria Publisher Pubmed



Philippot Q^{1, 2} ; Ogishi M³ ; Bohlen J^{1, 2} ; Puchan J⁴ ; Arias AA^{3, 5, 6} ; Nguyen T^{7, 8} ; Martinfernandez M^{9, 10, 11, 12, 13} ; Conil C^{1, 2} ; Rinchai D³ ; Momenilandi M^{1, 2} ; Mahdaviani SA¹⁴ ; Keramatipour M¹⁵ ; Rosain J^{1, 2} ; Yang R³ Show All Authors
Source: Science Immunology Published:2023

Abstract

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 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. Copyright © 2023 The Authors, some rights reserved.