Lack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)
Copyright © 2015 Elsevier Inc. All rights reserved.
Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 161(2015), 2 vom: 05. Dez., Seite 355-65 |
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Weitere Verfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2015
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Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
Schlagworte: | Journal Article Research Support, Non-U.S. Gov't CD127 CpG IL7Rα Promoter DNA methylation SIOD T-cell immunodeficiency Interleukin-17 Receptors, Interleukin-7 mehr... |
Zusammenfassung: | Copyright © 2015 Elsevier Inc. All rights reserved. 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 (IL7Rα) 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 IL7Rα expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients |
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Beschreibung: | Date Completed 14.03.2016 Date Revised 10.12.2019 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-7035 |
DOI: | 10.1016/j.clim.2015.10.005 |