Lack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)

Mrinmoy Sanyal, Marie Morimoto, Alireza Baradaran-Heravi, Kunho Choi, Neeraja Kambham, Kent Jensen, Suparna Dutt, Kira Y. Dionis-Petersen, Lan Xiang Liu, Katie Felix, Christy Mayfield, Benjamin Dekel, Arend Bokenkamp, Helen Fryssira, Encarna Guillen-Navarro, Giuliana Lama, Milena Brugnara, Thomas Lücke, Ann Haskins Olney, Tracy E. HunleyAyse Ipek Polat, Uluc Yis, Radovan Bogdanovic, Katarina Mitrovic, Susan Berry, Lydia Najera, Behzad Najafian, Mattia Gentile, C. Nur Semerci, Michel Tsimaratos, David B. Lewis, Cornelius F. Boerkoel

Research output: Contribution to journalArticle

7 Scopus citations

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 (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.

Original languageEnglish (US)
Pages (from-to)355-365
Number of pages11
JournalClinical Immunology
Volume161
Issue number2
DOIs
StatePublished - Dec 1 2015

Keywords

  • CD127
  • CpG
  • IL7Rα
  • Promoter DNA methylation
  • SIOD
  • T-cell immunodeficiency

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    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., Lücke, T., Olney, A. H., ... Boerkoel, C. F. (2015). Lack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD). Clinical Immunology, 161(2), 355-365. https://doi.org/10.1016/j.clim.2015.10.005