Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria
In: Cell, Jg. 186 (2023), Heft 23, S. 5114-5134
Online
academicJournal
- 21; Illustrationen
Zugriff:
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.
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Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria
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Autor/in / Beteiligte Person: | Bohlen, Jonathan, gnd_1181118379 ; Zhou, Qinhua ; Philippot, Quentin ; Ogishi, Masato ; Rinchai, Darawan ; Nieminen, Tea ; Seyedpour, Simin ; Parvaneh, Nima ; Rezaei, Nima, gnd_1065847335 ; Yazdanpanah, Niloufar ; Momenilandi, Mana ; Conil, Clément ; Neehus, Anna-Lena ; Schmidt, Carltin ; Arango-Franco, Carlos A ; Voyer, Tom Le ; Khan, Taushif ; Yang, Rui ; Puchan, Julia ; Erazo, Lucia ; Roiuk, Mykola, gnd_1257241885 ; Vatovec, Taja ; Janda, Zarah, gnd_1318837200 ; Bagarić, Ivan, gnd_1318840414 ; Materna, Marie ; Gervais, Adrian ; Liang, Hailun, gnd_1222773708 ; Rosain, Jérémie ; Peel, Jessica N ; Seeleuthner, Yoann ; Han, Ji Eun ; L’Honneur, Anne-Sophie ; Moncada-Vélez, Marcela ; Martin-Fernandez, Marta ; Horesh, Michael E ; Kochetkova, Tatiana, gnd_1310093717 ; Schmidt, Monika ; AlShehri, Mohammed A ; Salo, Eeva ; Saxen, Harri ; ElGhazali, Gehad ; Yatim, Ahmad ; Soudée, Camille ; Sallusto, Federica, gnd_1160257477 ; Ensser, Armin, gnd_1311449140 ; Marr, Nico, gnd_133189627 ; Zhang, Peng ; Bogunovic, Dusan ; Cobat, Aurélie ; Shahrooei, Mohammad ; Béziat, Vivien ; Abel, Laurent, gnd_144021587 ; Wang, Xiaochuan ; Boisson-Dupuis, Stéphanie ; Teleman, Aurelio A., gnd_1155118294 ; Bustamante, Jacinta ; Zhang, Qian ; Casanova, Jean-Laurent, gnd_144021471 |
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Zeitschrift: | Cell, Jg. 186 (2023), Heft 23, S. 5114-5134 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
Umfang: | 21; Illustrationen |
ISSN: | 1097-4172 (print) |
DOI: | 10.1016/j.cell.2023.09.024 |
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