Lack of IL7R alpha expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)
CLINICAL IMMUNOLOGY, cilt.161, sa.2, ss.355-365, 2015 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 161 Sayı: 2
- Basım Tarihi: 2015
- Doi Numarası: 10.1016/j.clim.2015.10.005
- Dergi Adı: CLINICAL IMMUNOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.355-365
- Anahtar Kelimeler: SIOD, T-cell immunodeficiency, IL7R alpha, CD127, CpG, Promoter DNA methylation
- Dokuz Eylül Üniversitesi Adresli: Evet
Özet
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.