Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria

Bohlen J, Enßer A, Zhou Q, Philippot Q, Ogishi M, Rinchai D, Nieminen T, Seyedpour S, Parvaneh N, Rezaei N, Yazdanpanah N, Momenilandi M, Conil C, Neehus AL, Schmidt C, Arango-Franco CA, Voyer TL, 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 JN, Seeleuthner Y, Han JE, L'Honneur AS, Moncada-Vélez M, Martin-Fernandez M, Horesh ME, Kochetkov T, Schmidt M, AlShehri MA, 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 AA, Bustamante J, Zhang Q, Casanova JL (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Cell Elsevier

Book Volume: 186

Pages Range: 5114-5134.e27

Journal Issue: 23

DOI: 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.

Authors with CRIS profile

Armin Enßer Institute of Clinical and Molecular Virology

Involved external institutions

Rockefeller University US United States (USA) (US) Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich CH Switzerland (CH) Hamad Bin Khalifa University QA Qatar (QA) Icahn School of Medicine at Mount Sinai US United States (USA) (US) Hôpital Necker-Enfants malades FR France (FR) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS) FI Finland (FI) Hôpital Cochin FR France (FR) King Fahad Medical City SA Saudi Arabia (SA) United Arab Emirates University / جامعة الإمارات العربية المتحدة AE United Arab Emirates (AE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) Fudan University / 复旦大学 CN China (CN)

How to cite

APA:

Bohlen, J., Enßer, A., Zhou, Q., Philippot, Q., Ogishi, M., Rinchai, D.,... Casanova, J.L. (2023). Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria. Cell, 186(23), 5114-5134.e27. https://doi.org/10.1016/j.cell.2023.09.024

MLA:

Bohlen, Jonathan, et al. "Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria." Cell 186.23 (2023): 5114-5134.e27.

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