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Title: | Haplotype 4 of the multiple sclerosis-associated interleukin-7 receptor alpha gene influences the frequency of recent thymic emigrants. | Authors: | BROUX, Bieke HELLINGS, Niels VENKEN, Koen RUMMENS, Jean-Luc HENSEN, Karen VAN WIJMEERSCH, Bart STINISSEN, Piet |
Issue Date: | 2010 | Publisher: | NATURE PUBLISHING GROUP | Source: | GENES AND IMMUNITY, 11(4). p. 323-336 | Abstract: | The receptor for the homeostatic T cell cytokine interleukin-7 (IL-7Ralpha) has recently shown genetic association to multiple sclerosis (MS). To investigate the functional contribution of IL-7Ralpha polymorphisms to the pathogenesis of MS, we correlated the IL-7Ralpha 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-7Ralpha haplotypes (Hap4) show a higher expression of IL-7Ralpha (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-7Ralpha polymorphisms can influence T cell development and homeostasis, and thereby contribute to the altered immune regulation associated with disease development in patients with MS.Genes and Immunity advance online publication, 14 January 2010; doi:10.1038/gene.2009.106. | Notes: | Biomedical Research Institute, Hasselt University and School of Life Sciences, transnationale Universiteit Limburg, Diepenbeek, Belgium. | Document URI: | http://hdl.handle.net/1942/10710 | ISSN: | 1466-4879 | e-ISSN: | 1476-5470 | DOI: | 10.1038/gene.2009.106 | ISI #: | 000278291000005 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2011 |
Appears in Collections: | Research publications |
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