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Haplotype 4 of the multiple sclerosis-associated interleukin-7 receptor alpha gene influences the frequency of recent thymic emigrants

Genes & Immunity volume 11, pages 326–333 (2010)Cite this article

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Abstract

The receptor for the homeostatic T cell cytokine interleukin-7 (IL-7Rα) has recently shown genetic association to multiple sclerosis (MS). To investigate the functional contribution of IL-7Rα polymorphisms to the pathogenesis of MS, we correlated the IL-7Rα haplotypes with different T cell parameters in a group of MS patients and healthy controls. We show that carriers of one of the four IL-7Rα haplotypes (Hap4) show a higher expression of IL-7Rα (CD127) on their CD4+ T cells, compared with noncarriers (P=0.04). Moreover, Hap4 carriers possess higher frequencies of recent thymic emigrants (RTEs, CD31+) in both the regulatory T cell (Treg; P=0.007) and conventional T cell (Tconv) population (P=0.0001). This effect is most pronounced within the MS population (Treg, P=0.0077; Tconv, P=0.0007), whereas in healthy controls significance was only reached for Tconv (P=0.043; Treg, P=0.11). Because previous studies showed a decreased RTE–Treg frequency in MS patients compared to healthy subjects, we here conclude that this decrease is localized within the MS population of non-Hap4 carriers. In conclusion, our findings suggest that IL-7Rα polymorphisms can influence T cell development and homeostasis, and thereby contribute to the altered immune regulation associated with disease development in patients with MS.

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Acknowledgements

We thank patients and healthy controls for blood donations, and Tom Broekmans and Anne Bogaers for assistance in collecting the blood samples. We also thank Hanne Jongen (the hematology unit of the Virga Jesse hospital, Hasselt) for performing flow cytometric analyses on FACSCanto.

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Authors and Affiliations

  1. Biomedical Research Institute, Hasselt University and School of Life Sciences, transnationale Universiteit Limburg, Diepenbeek, Belgium

    B Broux, N Hellings, B Van Wijmeersch & P Stinissen

  2. Department of Rheumatology, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, Gent, Belgium

    K Venken

  3. Clinical Laboratory of Experimental Hematology, Virga Jesse Hospital, Hasselt, Belgium

    J-L Rummens & K Hensen

  4. Mariaziekenhuis Noord-Limburg and Revalidatie & MS-Centrum, Overpelt, Belgium

    B Van Wijmeersch

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  1. B Broux
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  2. N Hellings
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  7. P Stinissen
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Correspondence to P Stinissen.

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Broux, B., Hellings, N., Venken, K. et al. Haplotype 4 of the multiple sclerosis-associated interleukin-7 receptor alpha gene influences the frequency of recent thymic emigrants. Genes Immun 11, 326–333 (2010). https://doi.org/10.1038/gene.2009.106

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  • DOI: https://doi.org/10.1038/gene.2009.106

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