Vollständiger Abstract
Worum geht es in dieser Arbeit?
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.
Bibliografischer Nachweis
Publikationsdaten
- Autor:innen
- Iris Fagniez, Miyuki Tsumura, Antoine Guérin, Hassan Abolhassani, Samin Sharafian, Mehrnaz Mesdaghi, Toyoki Nishimura, Harsha Prasada Lashkari, Sadashiva Rao, Stephanie Richards, Ji Eun Han, Ottavia M. Delmonte, Camille Kergaravat, Janet G. Markle, Masato Ogishi, Jing Han, Jessica Peel, Joseph Vellutini, Yi Feng, Camille Soudée, Mélanie Migaud, Boaz Palterer, Katherine J.L. Jackson, Shiho Nishimura, Sonoko Sakata, Keishiro Kinoshita, Ayako Yamamoto, Hiroshi Moritake, Mohammed Alzahrani, Francisco Vallejos, Theresa Cole, Joanne M. Smart, Sharon Choo, Zahra Chavoshzadeh, Shahnaz Armin, Antoine Toubert, Peng Zhang, Jérémie Rosain, Luigi D. Notarangelo, Qiang Pan-Hammarström
- Quelle
- Journal of Experimental Medicine
- Publikation
- 2026-09-04
- Band / Ausgabe
- 223 / 10
- Seiten
- Nicht angegeben
- ISSN / ISBN
- 0022-1007, 1540-9538
- Zitationen
- 0 laut Crossref
- Referenzen
- 115 hinterlegt
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Zitierfähiger Nachweis
Iris Fagniez, Miyuki Tsumura, Antoine Guérin, Hassan Abolhassani, Samin Sharafian, Mehrnaz Mesdaghi, Toyoki Nishimura, Harsha Prasada Lashkari, Sadashiva Rao, Stephanie Richards, Ji Eun Han, Ottavia M. Delmonte, Camille Kergaravat, Janet G. Markle, Masato Ogishi, Jing Han, Jessica Peel, Joseph Vellutini, Yi Feng, Camille Soudée, Mélanie Migaud, Boaz Palterer, Katherine J.L. Jackson, Shiho Nishimura, Sonoko Sakata, Keishiro Kinoshita, Ayako Yamamoto, Hiroshi Moritake, Mohammed Alzahrani, Francisco Vallejos, Theresa Cole, Joanne M. Smart, Sharon Choo, Zahra Chavoshzadeh, Shahnaz Armin, Antoine Toubert, Peng Zhang, Jérémie Rosain, Luigi D. Notarangelo, Qiang Pan-Hammarström (2026). Human-inherited RORγT deficiency encompasses genetic heterogeneity, T cell deficiency, and clinical homogeneity. Journal of Experimental Medicine, 223 (10). https://doi.org/10.1084/jem.20252038
Kontext
Themen, Förderung und Nutzung
Förderung: Howard Hughes Medical Institute, Rockefeller University, Institut National de la Santé et de la Recherche Médicale, Université Paris Cité, St. Giles Foundation, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences, National Institutes of Health, Immune Deficiency Foundation, Stony Wold-Herbert Fund, French National Research Agency, French Foundation for Medical Research, Square Foundation, Grandir - Fonds de solidarité pour l’enfance, Fondation du Souffle, King Baudouin Foundation, SCOR Corporate Foundation for Science, General Atlantic Foundation, Funai Foundation for Information Technology, New York Hideyo Noguchi Memorial Society
Lizenzhinweise: Lizenz 1