Lack of IL7R alpha expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)

Autor:	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
Přispěvatelé:	Pediatric surgery, ICaR - Circulation and metabolism
Rok vydání:	2015
Předmět:	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
Zdroj:	Clinical Immunology, 161(2), 355-365. Academic Press Inc. Sanyal, M, Morimoto, M, Baradaran-Heravi, A, Choi, K, Kambham, N, Jensen, K, Dutt, S, Dionis-Petersen, K Y, Liu, L X, Felix, K, Mayfield, C, Dekel, B, Bokenkamp, A, Fryssira, H, Guillen-Navarro, E, Lama, G, Brugnara, M, Lucke, T, Olney, A H, Hunley, T E, Polat, A I, Yis, U, Bogdanovic, R, Mitrovic, K, Berry, S, Najera, L, Najafian, B, Gentile, M, Semerci, C N, Tsimaratos, M, Lewis, D B & Boerkoel, C F 2015, ' Lack of IL7R alpha expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD) ', Clinical Immunology, vol. 161, no. 2, pp. 355-365 . https://doi.org/10.1016/j.clim.2015.10.005
ISSN:	1521-6616
DOI:	10.1016/j.clim.2015.10.005
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f50c6086f08104dec7b390962062b36b https://doi.org/10.1016/j.clim.2015.10.005 Zobrazit plný text záznamu Full Text from ScienceDirect