1. Lack of IL7R alpha expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)
- Author
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Arend Bökenkamp, Kira Y. Dionis-Petersen, Lan Xiang Liu, Neeraja Kambham, Helen Fryssira, Ayşe İpek Polat, Mattia Gentile, C. Nur Semerci, Tracy E. Hunley, Katarina Mitrovic, Behzad Najafian, Radovan Bogdanovic, Mrinmoy Sanyal, Uluç Yiş, Encarna Guillen-Navarro, Katie Felix, Marie Morimoto, Christy Mayfield, Alireza Baradaran-Heravi, Thomas Lücke, Susan A. Berry, Cornelius F. Boerkoel, David B. Lewis, Kent P. Jensen, Kunho Choi, Lydia Najera, Giuliana Lama, Suparna Dutt, Michel Tsimaratos, Ann Haskins Olney, Benjamin Dekel, Milena Brugnara, Pediatric surgery, and ICaR - Circulation and metabolism
- Subjects
Nephrotic Syndrome ,SMARCAL1 protein, human ,Arteriosclerosis ,T-Lymphocytes ,interleukin 7 receptor alpha ,Gene Expression ,Gene mutation ,SIOD ,preschool child ,T-cell immunodeficiency ,0302 clinical medicine ,chondrodysplasia ,mononuclear cell ,T lymphocyte ,Immunology and Allergy ,genetics ,exon ,gene mutation ,Child ,Promoter Regions, Genetic ,Immunodeficiency ,Cells, Cultured ,0303 health sciences ,clinical article ,DNA methylation ,messenger RNA ,Reverse Transcriptase Polymerase Chain Reaction ,adult ,Interleukin-17 ,Flow Cytometry ,Immunohistochemistry ,IL7R? ,3. Good health ,Adolescent ,Adult ,Arteriosclerosis/*genetics/metabolism/pathology ,Child, Preschool ,DNA Helicases/genetics ,DNA Methylation ,Humans ,Immunologic Deficiency Syndromes/*genetics/metabolism/pathology ,Interleukin-17/pharmacology ,Leukocytes, Mononuclear/drug effects/metabolism ,Mutation ,Nephrotic Syndrome/*genetics/metabolism/pathology ,Osteochondrodysplasias/*genetics/metabolism/pathology ,Primary Immunodeficiency Di ,priority journal ,young adult ,Interleukin 17 ,schimke immuno osseous dysplasia ,T-Cell Immunodeficiency ,IL7Rα ,lung embolism ,Primary Immunodeficiency Diseases ,Immunology ,interleukin-7 receptor, alpha chain ,DNA sequence ,DNA helicase ,Biology ,interleukin 7 ,Osteochondrodysplasias ,Article ,Promoter DNA methylation ,reverse transcription polymerase chain reaction ,03 medical and health sciences ,promoter region ,CpG ,medicine ,controlled study ,human ,Interleukin-7 receptor ,protein expression ,030304 developmental biology ,cell culture ,Receptors, Interleukin-7 ,autosomal recessive disorder ,human cell ,Schimke immuno-osseous dysplasia ,DNA Helicases ,Immunologic Deficiency Syndromes ,Sequence Analysis, DNA ,immune deficiency ,medicine.disease ,school child ,human tissue ,CD127 ,Dysplasia ,interleukin 7 receptor ,drug effects ,Leukocytes, Mononuclear ,pathology ,interleukin 17 ,Pulmonary Embolism ,metabolism ,030217 neurology & neurosurgery - Abstract
Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal childhood disorder associated with skeletal dysplasia, renal dysfunction, and T-cell immunodeficiency. This disease is linked to biallelic loss-of-function mutations of the SMARCAL1 gene. Although recurrent infection, due to T-cell deficiency, is a leading cause of morbidity and mortality, the etiology of the T-cell immunodeficiency is unclear. Here, we demonstrate that the T cells of SIOD patients have undetectable levels of protein and mRNA for the IL-7 receptor alpha chain (IL7R alpha) and are unresponsive to stimulation with IL-7, indicating a loss of functional receptor. No pathogenic mutations were detected in the exons of IL7R in these patients; however, CpG sites in the IL7R promoter were hypermethylated in SIOD T cells. We propose therefore that the lack of IL7R alpha expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients. (C) 2015 Elsevier Inc. All rights reserved.
- Published
- 2015