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

• DOI: 10.1016/j.cell.2023.09.024
• Publication Date: 2023-10-23T14:28:43Z
• Authors: Jonathan Bohlen; Qinhua Zhou; Quentin Philippot; Masato Ogishi; Darawan Rinchai; Tea Nieminen; Simin Seyedpour; Nima Parvaneh; Nima Rezaei; Niloufar Yazdanpanah; Mana Momenilandi; Clément Conil; Anna-Lena Neehus; Carltin Schmidt; Carlos A. Arango-...; Tom Le Voyer; Taushif Khan; Rui Yang; Julia Puchan; Lucia Erazo; Mykola Roiuk; Taja Vatovec; Zarah Janda; Ivan Bagarić; Marie Materna; Adrian Gervais; Hailun Li; Jérémie Rosain; Jessica N Peel; Yoann Seeleuthner; Ji Eun Han; Anne-Sophie L’Hon...; Marcela Moncada-V...; Marta Martin-Fern...; Michael E. Horesh; Tatiana Kochetkov; Monika Schmidt; Mohammed A. AlShehri; Eeva Salo; Harri Saxen; Gehad ElGhazali; Ahmad Yatim; Camille Soudée; Federica Sallusto; Armin Ensser; Nico Marr; Peng Zhang; Dusan Bogunovic; Aurélie Cobat; Mohammad Shahrooei; Vivien Béziat; Laurent Abel; Xiaochuan Wang; Stéphanie Boisson...; Aurelio A. Teleman; Jacinta Bustamante; Qian Zhang; Jean-Laurent Casa...
• Keywords: Male; INBORN-ERRORS; Human Inborn Errors; Translation (biology); Cell Cycle Proteins; SUSCEPTIBILITY; Interleukin-23; Gene; mycobacterium; inborn error of immunity; IL-23; Pathogenesis and Treatment of Whipple's Disease; Interferon gamma; Oncogene Proteins; Immunology and Microbiology; TYROSINE PHOSPHORYLATION; JGM; Innate immune system; Messenger RNA; Life Sciences; Interleukin-12; 3. Good health; GENETIC DISSECTION; READ ALIGNMENT; MSMD; DEFICIENCY; JAK2; Medicine; Interferon; INTERFERON-GAMMA-RECEPTOR; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; translation re-initiation; Immunology; 610; HUMAN MACROPHAGES; Article; Mycobacterium; Pathology and Forensic Medicine; Interferon-gamma; X-linked disease; Virology; Health Sciences; Genetics; BACILLE CALMETTE-GUERIN; Humans; MCTS1; Biology; Cytokine; Biochemistry, cell and molecular biology; Mycobacterium Infections; Science & Technology; Genetic Basis of Primary Immunodeficiency Disorders; FOS: Clinical medicine; Immunity; Cell Biology; Acquired immune system; Janus Kinase 2; INTERLEUKIN-12; Immune system; FOS: Biological sciences; Natural Killer Cells in Immunity

Human inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with disease from kindreds different ancestries (from China, Finland, Iran, and Saudi Arabia). Complete this translation re-initiation factor impairs the a subset proteins, including kinase JAK2 all cell types tested, T lymphocytes phagocytes. expression is sufficiently low to impair cellular responses interleukin-23 (IL-23) partially IL-12, but not other JAK2-dependent cytokines. Defective IL-23 preferentially production IFN-γ by innate-like adaptive mucosal-associated invariant cells (MAIT) γδ upon challenge. Surprisingly, lack MCTS1-dependent ribosome recycling seems be otherwise physiologically redundant these patients. These findings suggest that human underlies isolated impairing lymphocytes, thereby IL-23-dependent induction IFN-γ.