Nature Communications (Jul 2019)
Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis
- Nina K. Serwas,
- Birgit Hoeger,
- Rico C. Ardy,
- Sigrun V. Stulz,
- Zhenhua Sui,
- Nima Memaran,
- Marie Meeths,
- Ana Krolo,
- Özlem Yüce Petronczki,
- Laurène Pfajfer,
- Tie Z. Hou,
- Neil Halliday,
- Elisangela Santos-Valente,
- Artem Kalinichenko,
- Alan Kennedy,
- Emily M. Mace,
- Malini Mukherjee,
- Bianca Tesi,
- Anna Schrempf,
- Winfried F. Pickl,
- Joanna I. Loizou,
- Renate Kain,
- Bettina Bidmon-Fliegenschnee,
- Jean-Nicolas Schickel,
- Salomé Glauzy,
- Jakob Huemer,
- Wojciech Garncarz,
- Elisabeth Salzer,
- Iro Pierides,
- Ivan Bilic,
- Jens Thiel,
- Peter Priftakis,
- Pinaki P. Banerjee,
- Elisabeth Förster-Waldl,
- David Medgyesi,
- Wolf-Dietrich Huber,
- Jordan S. Orange,
- Eric Meffre,
- David M. Sansom,
- Yenan T. Bryceson,
- Amnon Altman,
- Kaan Boztug
Affiliations
- Nina K. Serwas
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Birgit Hoeger
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Rico C. Ardy
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Sigrun V. Stulz
- Centre for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge
- Zhenhua Sui
- Division of Cell Biology, La Jolla Institute for Allergy & Immunology
- Nima Memaran
- Department of Pediatrics and Adolescent Medicine, Medical University of Vienna
- Marie Meeths
- Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital Solna
- Ana Krolo
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Özlem Yüce Petronczki
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Laurène Pfajfer
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Tie Z. Hou
- Institute of Immunity and Transplantation, Division of Infection & Immunity, School of Life and Medical Sciences, University College London
- Neil Halliday
- Institute of Immunity and Transplantation, Division of Infection & Immunity, School of Life and Medical Sciences, University College London
- Elisangela Santos-Valente
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Artem Kalinichenko
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Alan Kennedy
- Institute of Immunity and Transplantation, Division of Infection & Immunity, School of Life and Medical Sciences, University College London
- Emily M. Mace
- Department of Pediatrics, Baylor College of Medicine and Center for Human Immunobiology, Texas Children’s Hospital
- Malini Mukherjee
- Department of Pediatrics, Baylor College of Medicine and Center for Human Immunobiology, Texas Children’s Hospital
- Bianca Tesi
- Clinical Genetics Unit, Department of Molecular Medicine and Surgery, and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna
- Anna Schrempf
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Winfried F. Pickl
- Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna
- Joanna I. Loizou
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Renate Kain
- Clinical Institute of Pathology, Medical University of Vienna
- Bettina Bidmon-Fliegenschnee
- Department of Pediatrics and Adolescent Medicine, Medical University of Vienna
- Jean-Nicolas Schickel
- Department of Immunobiology, Yale University School of Medicine
- Salomé Glauzy
- Department of Immunobiology, Yale University School of Medicine
- Jakob Huemer
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Wojciech Garncarz
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Elisabeth Salzer
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Iro Pierides
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Ivan Bilic
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Jens Thiel
- Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg
- Peter Priftakis
- Astrid Lindgren Children’s Hospital, Karolinska University Hospital Huddinge
- Pinaki P. Banerjee
- Department of Pediatrics, Baylor College of Medicine and Center for Human Immunobiology, Texas Children’s Hospital
- Elisabeth Förster-Waldl
- Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna
- David Medgyesi
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- Wolf-Dietrich Huber
- Department of Pediatrics and Adolescent Medicine, Medical University of Vienna
- Jordan S. Orange
- Department of Pediatrics, Baylor College of Medicine and Center for Human Immunobiology, Texas Children’s Hospital
- Eric Meffre
- Department of Immunobiology, Yale University School of Medicine
- David M. Sansom
- Institute of Immunity and Transplantation, Division of Infection & Immunity, School of Life and Medical Sciences, University College London
- Yenan T. Bryceson
- Centre for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge
- Amnon Altman
- Division of Cell Biology, La Jolla Institute for Allergy & Immunology
- Kaan Boztug
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
- DOI
- https://doi.org/10.1038/s41467-019-10812-x
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 15
Abstract
CTLA-4 is critical for balancing protective immunity with self-tolerance. Here the authors identify homozygous DEF6 mutations in patients with severe autoimmunity, one of which received and responds to CTLA-4-Ig, and show that DEF6 is crucial for CTLA-4 cell surface trafficking and immune regulatory function.
