Document Type
Article
Publication Date
11-9-2023
Original Citation
Bohlen J,
Zhou Q,
Philippot Q,
Ogishi M,
Rinchai D,
Nieminen T,
Seyedpour S,
Parvaneh N,
Rezaei N,
Yazdanpanah N,
Momenilandi M,
Conil C,
Neehus A,
Schmidt C,
Arango-Franco C,
Voyer T,
Khan T,
Yang R,
Puchan J,
Erazo L,
Roiuk M,
Vatovec T,
Janda Z,
Bagarić I,
Materna M,
Gervais A,
Li H,
Rosain J,
Peel J,
Seeleuthner Y,
Han J,
L'Honneur A,
Moncada-Vélez M,
Martin-Fernandez M,
Horesh M,
Kochetkov T,
Schmidt M,
AlShehri M,
Salo E,
Saxen H,
ElGhazali G,
Yatim A,
Soudée C,
Sallusto F,
Ensser A,
Marr N,
Zhang P,
Bogunovic D,
Cobat A,
Shahrooei M,
Béziat V,
Abel L,
Wang X,
Boisson-Dupuis S,
Teleman A,
Bustamante J,
Zhang Q,
Casanova J.
Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria. Cell. 2023;186(23):5114-34.
Keywords
JGM, Humans, Male, Cell Cycle Proteins, Interferon-gamma, Interleukin-12, Interleukin-23, Janus Kinase 2, Mycobacterium, Mycobacterium Infections, Oncogene Proteins
JAX Source
Cell. 2023;186(23):5114-34.
ISSN
1097-4172
PMID
37875108
DOI
https://doi.org/10.1016/j.cell.2023.09.024
Abstract
Human inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with mycobacterial disease from kindreds of different ancestries (from China, Finland, Iran, and Saudi Arabia). Complete deficiency of this translation re-initiation factor impairs the translation of a subset of proteins, including the kinase JAK2 in all cell types tested, including T lymphocytes and phagocytes. JAK2 expression is sufficiently low to impair cellular responses to interleukin-23 (IL-23) and partially IL-12, but not other JAK2-dependent cytokines. Defective responses to IL-23 preferentially impair the production of IFN-γ by innate-like adaptive mucosal-associated invariant T cells (MAIT) and γδ T lymphocytes upon mycobacterial challenge. Surprisingly, the lack of MCTS1-dependent translation re-initiation and ribosome recycling seems to be otherwise physiologically redundant in these patients. These findings suggest that X-linked recessive human MCTS1 deficiency underlies isolated mycobacterial disease by impairing JAK2 translation in innate-like adaptive T lymphocytes, thereby impairing the IL-23-dependent induction of IFN-γ.
Comments
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).