Polymorphisms (single-nucleotide polymorphism (SNP)) in the
interleukin-7 receptor-α (IL-7Rα)/IL-7 pathway are associated with an
increased risk to develop multiple sclerosis
(MS). The rs6897932 SNP in the IL-7Rα leads to increased soluble IL-7Rα
production. Given the functional interaction between sIL-7Rα,
membrane-bound IL-7Rα and IL-7, we assessed IL-7, mIL-7Rα and sIL-7Rα
levels in MS patients and healthy controls (HCs). One-hundred and twenty
eight MS patients had significantly lower sIL-7Rα levels compared with
73 HCs. The levels of sIL-7Rα increased dose-dependent upon rs6897932
[C] risk allele carriership in both HCs and MS. Next, we hypothesized
that lower sIL-7Rα could result in a higher mIL-7Rα to soluble IL-7Rα
ratio. Indeed, 52 MS patients had significantly increased mIL-7Rα to
sIL-7Rα ratio for both CD4 and CD8 T cells compared with 44 HCs. Given
the supposed role of IL-7 in autoimmunity, we determined whether sIL-7Rα
influences IL-7 levels. IL-7 levels were significantly decreased in 40
MS patients compared with 40 HCs. In conclusion, MS patients had lower
free IL-7 and a higher membrane to soluble IL-7Rα ratio. The soluble
IL-7Rα levels correlate with the rs6897932 [C] risk allele carriership.
The skew at the IL-7 and IL-7Rα level may influence responsiveness of
IL-7Rα(+) cells
Genes relating to the interleukin 7 receptor, which binds interleukin 7 (IL-7), which is a white blood cell growth factor are linked to the susceptibility of MS. When IL-7 receptor (soluble IL-7R) is shed from cells if floats around the blood mopping up IL-7. The genetic variant as receptorsocated with MS leads to an increase in the production of the shedv version of IL-7 receptor and indeed people with MS had lower IL-7 in their blood. HOw this actually influences MS is unknown but it is likely going to be something to do with the development of the immune response.
Labels: IL-7 receptor