Academic Journal
Human inherited RORγT deficiency encompasses genetic heterogeneity, T cell deficiency, and clinical homogeneity.
| Τίτλος: | Human inherited RORγT deficiency encompasses genetic heterogeneity, T cell deficiency, and clinical homogeneity. |
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| Συγγραφείς: | Fagniez I; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Tsumura M; Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan., Guérin A; Garvan Institute of Medical Research , Sydney, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, UNSW Sydney, Sydney, Australia., Abolhassani H; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children´s Medical Center, Tehran University of Medical Sciences , Tehran, Iran., Sharafian S; Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Mesdaghi M; Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Nishimura T; Division of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki City, Japan., Lashkari HP; Department of Pediatrics, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India., Rao S; Department of Surgery, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India., Richards S; Allergy & Immunology, Royal Children's Hospital, Melbourne, Australia., Han JE; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Delmonte OM; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Kergaravat C; Institut de Recherche Saint Louis, INSERM UMR 1342, Université Paris Cité , Paris, France., Markle JG; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Department of Pathology Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Ogishi M; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Han J; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Peel J; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Vellutini J; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Feng Y; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Soudée C; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Université Paris Cité , Paris, France., Migaud M; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Université Paris Cité , Paris, France., Palterer B; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Jackson KJL; Garvan Institute of Medical Research , Sydney, Australia., Nishimura S; Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan., Sakata S; Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan., Kinoshita K; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Yamamoto A; Division of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki City, Japan., Moritake H; Division of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki City, Japan., Alzahrani M; Department of Pediatrics, Security Forces Hospital, Riyadh, Saudi Arabia., Vallejos F; Division of Pediatric Immunology, Gustavo Fricke Hospital, Valparaiso, Chile., Cole T; Allergy & Immunology, Royal Children's Hospital, Melbourne, Australia., Smart JM; Allergy & Immunology, Royal Children's Hospital, Melbourne, Australia., Choo S; Allergy & Immunology, Royal Children's Hospital, Melbourne, Australia., Chavoshzadeh Z; Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Armin S; Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences , Tehran, Iran., Toubert A; Institut de Recherche Saint Louis, INSERM UMR 1342, Université Paris Cité , Paris, France., Zhang P; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Université Paris Cité , Paris, France., Rosain J; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Université Paris Cité , Paris, France.; Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (AP-HP) , Paris, France., Notarangelo LD; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Pan-Hammarström Q; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden., Tangye SG; Garvan Institute of Medical Research , Sydney, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, UNSW Sydney, Sydney, Australia., Casanova JL; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Université Paris Cité , Paris, France.; Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (AP-HP) , Paris, France.; Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France.; Howard Hughes Medical Institute , New York, NY, USA., Ma CS; Garvan Institute of Medical Research , Sydney, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, UNSW Sydney, Sydney, Australia., Puel A; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Université Paris Cité , Paris, France., Bustamante J; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Université Paris Cité , Paris, France.; Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (AP-HP) , Paris, France., Okada S; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan., Boisson-Dupuis S; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Université Paris Cité , Paris, France., Yang R; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Department of Pediatrics, Division of Immunology, Allergy, and Retrovirology, Baylor College of Medicine, Houston, TX, USA.; William T. Shearer Center for Human Immunobiology, Texas Children's Hospital , Houston, TX, USA. |
| Πηγή: | The Journal of experimental medicine [J Exp Med] 2026 Oct 05; Vol. 223 (10). Date of Electronic Publication: 2026 Sep 04. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York, NY : Rockefeller University Press |
| Ιατρικοί όροι (MeSH): | Nuclear Receptor Subfamily 1, Group F, Member 3*/deficiency , Nuclear Receptor Subfamily 1, Group F, Member 3*/genetics , Candidiasis, Chronic Mucocutaneous*/genetics , Candidiasis, Chronic Mucocutaneous*/immunology , T-Lymphocytes*/immunology , Genetic Heterogeneity*, Mycobacterium Infections/genetics ; Mycobacterium Infections/immunology ; Killer Cells, Natural/immunology ; Humans ; Male ; Female ; Child ; Child, Preschool ; Adolescent ; Young Adult |
| Περίληψη: | We previously reported inherited retinoic acid-related orphan receptor γ T (RORγT) deficiency in seven patients from three ancestries (Chilean, Palestinian, and Saudi Arabian) with mycobacterial disease and chronic mucocutaneous candidiasis (CMC). We report here five additional patients from different ancestries (Afghan, Indian, Iranian, Japanese, and Sri Lankan), each homozygous for a new loss-of-function RORC variant. All but one patient-the exception receiving early prophylaxis-developed mycobacterial disease due to a near-complete depletion of innate-like adaptive T cells, including mucosa-associated invariant T and invariant natural killer T cells, low counts of adaptive TH1* and CD8+ T cells, and impaired Mycobacterium-induced IFN-γ production by the remaining cells of these subsets, NK cells, conventional CD4+ T, Vδ1, and Vδ2 γδT cells. Most patients also displayed CMC due to their low counts of TH17 and TH1* cells. One patient died from disseminated Bacille Calmette-Guérin vaccine infection, but, unexpectedly, all the other patients are still alive and clinically stable at ages of 2 to 20 years. RORγT is essential for protective immunity against mycobacteria and Candida in humans. (© 2026 Fagniez et al.) |
| Σχόλια: | Update of: medRxiv. 2026 Jul 20:2026.07.18.26358075. doi: 10.64898/2026.07.18.26358075.. (PMID: 42539146) |
| Grant Information: | Université Paris Cité; Rockefeller University; R01 AI095983 United States AI NIAID NIH HHS; KAW 2023.0343 Knut and Alice Wallenberg Foundation; Grandir - Fonds de solidarité pour l'enfance; U19 AI162568 United States AI NIAID NIH HHS; ANR-10-LABX-62-IBEID French National Research Agency; Funai Foundation for Information Technology; 2017463 National Health and Medical Research Council; R01 AI127564 United States AI NIAID NIH HHS; JP25ek0109623 Japan Agency for Medical Research and Development; Ministry of Education, Culture, Sports, Science and Technology; New York Hideyo Noguchi Memorial Society; R01AI095983 National Institute of Allergy and Infectious Diseases; 22KK0113 Japan Society for the Promotion of Science; ECTZ170784-ANRS0073 Agence Nationale de Recherches sur le Sida et les Hépatites Virales; Stony Wold-Herbert Fund; JP25ek01975 Japan Agency for Medical Research and Development; Immune Deficiency Foundation; KAW 2020.0101 Knut and Alice Wallenberg Foundation; ANR-22-CE92-0008 French National Research Agency; JP256f0137011 Japan Agency for Medical Research and Development; EQU202503020018 French Foundation for Medical Research; UL1TR001866 United States TR NCATS NIH HHS; UL1 TR001866 United States TR NCATS NIH HHS; 22H03041 Japan Society for the Promotion of Science; UL1TR001866 United States NH NIH HHS; Institut National de la Santé et de la Recherche Médicale; United States HHMI Howard Hughes Medical Institute; Square Foundation; JPJS00420230011 Japan Society for the Promotion of Science; King Baudouin Foundation; U19AI162568 National Institute of Allergy and Infectious Diseases; Honjo International Scholarship Foundation; Fondation du Souffle; SCOR Corporate Foundation for Science; St. Giles Foundation; 1176665 National Health and Medical Research Council; Swedish Research Council; General Atlantic Foundation; R01AI127564 National Institute of Allergy and Infectious Diseases; ANR-10-IAHU-01 French National Research Agency; ANR-18-CE93-0008 French National Research Agency |
| Substance Nomenclature: | 0 (Nuclear Receptor Subfamily 1, Group F, Member 3) 0 (RORC protein, human) |
| Entry Date(s): | Date Created: 20260904 Date Completed: 20260904 Latest Revision: 20260930 |
| Update Code: | 20260930 |
| DOI: | 10.1084/jem.20252038 |
| PMID: | 42695969 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1540-9538 |
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| DOI: | 10.1084/jem.20252038 |