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

(2010) GENES AND IMMUNITY. 11(4). p.326-333
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Abstract
The receptor for the homeostatic T cell cytokine interleukin-7 (IL-7R alpha) has recently shown genetic association to multiple sclerosis (MS). To investigate the functional contribution of IL-7R alpha polymorphisms to the pathogenesis of MS, we correlated the IL-7R alpha 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-7R alpha haplotypes (Hap4) show a higher expression of IL-7R alpha (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-7Ra polymorphisms can influence T cell development and homeostasis, and thereby contribute to the altered immune regulation associated with disease development in patients with MS.
Keywords
multiple sclerosis, REGULATORY T-CELLS, recent thymic emigrants, polymorphism, interleukin-7 receptor, SUPPRESSIVE FUNCTION, AUTOIMMUNE-DISEASE, DENDRITIC CELLS, EXPRESSION, SUSCEPTIBILITY, RISK, ALLELES, INDUCE, BLOOD

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Chicago
Broux, B, Niels Hellings, Koen Venken, Jean-Luc Rummens, Karen Hensen, B Van Wijmeersch, and Piet Stinissen. 2010. “Haplotype 4 of the Multiple Sclerosis-associated Interleukin-7 Receptor Alpha Gene Influences the Frequency of Recent Thymic Emigrants.” Genes and Immunity 11 (4): 326–333.
APA
Broux, B, Hellings, N., Venken, K., Rummens, J.-L., Hensen, K., Van Wijmeersch, B., & Stinissen, P. (2010). Haplotype 4 of the multiple sclerosis-associated interleukin-7 receptor alpha gene influences the frequency of recent thymic emigrants. GENES AND IMMUNITY, 11(4), 326–333.
Vancouver
1.
Broux B, Hellings N, Venken K, Rummens J-L, Hensen K, Van Wijmeersch B, et al. Haplotype 4 of the multiple sclerosis-associated interleukin-7 receptor alpha gene influences the frequency of recent thymic emigrants. GENES AND IMMUNITY. 2010;11(4):326–33.
MLA
Broux, B, Niels Hellings, Koen Venken, et al. “Haplotype 4 of the Multiple Sclerosis-associated Interleukin-7 Receptor Alpha Gene Influences the Frequency of Recent Thymic Emigrants.” GENES AND IMMUNITY 11.4 (2010): 326–333. Print.
@article{2071034,
  abstract     = {The receptor for the homeostatic T cell cytokine interleukin-7 (IL-7R alpha) has recently shown genetic association to multiple sclerosis (MS). To investigate the functional contribution of IL-7R alpha polymorphisms to the pathogenesis of MS, we correlated the IL-7R alpha 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-7R alpha haplotypes (Hap4) show a higher expression of IL-7R alpha (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-7Ra polymorphisms can influence T cell development and homeostasis, and thereby contribute to the altered immune regulation associated with disease development in patients with MS.},
  author       = {Broux, B and Hellings, Niels and Venken, Koen and Rummens, Jean-Luc and Hensen, Karen and Van Wijmeersch, B and Stinissen, Piet},
  issn         = {1466-4879},
  journal      = {GENES AND IMMUNITY},
  keywords     = {multiple sclerosis,REGULATORY T-CELLS,recent thymic emigrants,polymorphism,interleukin-7 receptor,SUPPRESSIVE FUNCTION,AUTOIMMUNE-DISEASE,DENDRITIC CELLS,EXPRESSION,SUSCEPTIBILITY,RISK,ALLELES,INDUCE,BLOOD},
  language     = {eng},
  number       = {4},
  pages        = {326--333},
  title        = {Haplotype 4 of the multiple sclerosis-associated interleukin-7 receptor alpha gene influences the frequency of recent thymic emigrants},
  url          = {http://dx.doi.org/10.1038/gene.2009.106},
  volume       = {11},
  year         = {2010},
}

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