Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis
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...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2019-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-019-10812-x |
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| language |
English |
| format |
Article |
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DOAJ |
| author |
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 |
| spellingShingle |
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 Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis Nature Communications |
| author_facet |
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 |
| author_sort |
Nina K. Serwas |
| title |
Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis |
| title_short |
Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis |
| title_full |
Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis |
| title_fullStr |
Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis |
| title_full_unstemmed |
Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis |
| title_sort |
human def6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant ctla-4 homeostasis |
| publisher |
Nature Publishing Group |
| series |
Nature Communications |
| issn |
2041-1723 |
| publishDate |
2019-07-01 |
| description |
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. |
| url |
https://doi.org/10.1038/s41467-019-10812-x |
| work_keys_str_mv |
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doaj-2b28c1d1ae924d86a02c99db5aac2d802021-05-11T12:41:44ZengNature Publishing GroupNature Communications2041-17232019-07-0110111510.1038/s41467-019-10812-xHuman DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasisNina K. Serwas0Birgit Hoeger1Rico C. Ardy2Sigrun V. Stulz3Zhenhua Sui4Nima Memaran5Marie Meeths6Ana Krolo7Özlem Yüce Petronczki8Laurène Pfajfer9Tie Z. Hou10Neil Halliday11Elisangela Santos-Valente12Artem Kalinichenko13Alan Kennedy14Emily M. Mace15Malini Mukherjee16Bianca Tesi17Anna Schrempf18Winfried F. Pickl19Joanna I. Loizou20Renate Kain21Bettina Bidmon-Fliegenschnee22Jean-Nicolas Schickel23Salomé Glauzy24Jakob Huemer25Wojciech Garncarz26Elisabeth Salzer27Iro Pierides28Ivan Bilic29Jens Thiel30Peter Priftakis31Pinaki P. Banerjee32Elisabeth Förster-Waldl33David Medgyesi34Wolf-Dietrich Huber35Jordan S. Orange36Eric Meffre37David M. Sansom38Yenan T. Bryceson39Amnon Altman40Kaan Boztug41Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesCentre for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital HuddingeDivision of Cell Biology, La Jolla Institute for Allergy & ImmunologyDepartment of Pediatrics and Adolescent Medicine, Medical University of ViennaChildhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital SolnaLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesInstitute of Immunity and Transplantation, Division of Infection & Immunity, School of Life and Medical Sciences, University College LondonInstitute of Immunity and Transplantation, Division of Infection & Immunity, School of Life and Medical Sciences, University College LondonCeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesInstitute of Immunity and Transplantation, Division of Infection & Immunity, School of Life and Medical Sciences, University College LondonDepartment of Pediatrics, Baylor College of Medicine and Center for Human Immunobiology, Texas Children’s HospitalDepartment of Pediatrics, Baylor College of Medicine and Center for Human Immunobiology, Texas Children’s HospitalClinical Genetics Unit, Department of Molecular Medicine and Surgery, and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital SolnaCeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesInstitute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaCeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesClinical Institute of Pathology, Medical University of ViennaDepartment of Pediatrics and Adolescent Medicine, Medical University of ViennaDepartment of Immunobiology, Yale University School of MedicineDepartment of Immunobiology, Yale University School of MedicineLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesCeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesDepartment of Rheumatology and Clinical Immunology, University Medical Center FreiburgAstrid Lindgren Children’s Hospital, Karolinska University Hospital HuddingeDepartment of Pediatrics, Baylor College of Medicine and Center for Human Immunobiology, Texas Children’s HospitalDepartment of Pediatrics and Adolescent Medicine, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Medical University of ViennaLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesDepartment of Pediatrics and Adolescent Medicine, Medical University of ViennaDepartment of Pediatrics, Baylor College of Medicine and Center for Human Immunobiology, Texas Children’s HospitalDepartment of Immunobiology, Yale University School of MedicineInstitute of Immunity and Transplantation, Division of Infection & Immunity, School of Life and Medical Sciences, University College LondonCentre for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital HuddingeDivision of Cell Biology, La Jolla Institute for Allergy & ImmunologyLudwig Boltzmann Institute for Rare and Undiagnosed DiseasesCTLA-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.https://doi.org/10.1038/s41467-019-10812-x |