In summary, our findings indicate an augmented type-17 differentiation of MAIT cells in MS patients associated with their IL-7 receptor surface expression, implicating a proinflammatory role of these unconventional T cells in MS immunopathology.
Combination of IL-7 and CXCL10 indicated risk for a specific MS clinical form, where IL-7<141 and CXCL10<570pg/ml were associated with the highest risk for PP-MS (OR=22, p=0.01).
IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes.
The T-allele in the single nucleotide polymorphism rs6897932 in the gene encoding the IL-7 receptor α (IL7RA) is associated with reduced risk of autoimmune diseases including multiple sclerosis and also affects the course of HIV infection.
The IL-7/IL-7R signaling axis participates in cell survival, and perturbation of this pathway has been associated with enhanced susceptibility to MS. A link between IL-23-driven pathogenic T cells and IL-7/IL-7R signaling has previously been proposed, but has not been formally addressed.
Increased expression of IL-7 in the central nervous system as well as in peripheral immune cells is associated with multiple sclerosis and experimental allergic encephalomyelitis.
Former studies demonstrated the single nucleotide polymorphism (SNP) rs6897932 C/T in the IL-7 receptor (IL-7R) gene was associated with susceptibility to autoimmune diseases, including multiple sclerosis and type I diabetes.
We found reduced IL-7Rα expression on conventional T cells and upregulated IL-7 plasma levels together with reduction of RTE-Treg frequencies and Treg function in MS, without clear genetic influence.
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.
We measured the relative distribution of IL-7 and IL-7R spliced mRNA from patients with MS and healthy individuals and observed extensive alternative splicing of both genes with marked differences in proportional transcript expression levels.
Common genetic variants of IL-7 receptor alpha (IL-7Ralpha) have recently been shown to affect susceptibility to multiple sclerosis (MS) and type 1 diabetes, and survival following bone marrow transplantation.
In addition, we report altered expression of the genes encoding IL7Ralpha and its ligand, IL7, in the cerebrospinal fluid compartment of individuals with multiple sclerosis.