Functional role of multiple sclerosis-associated haplotypes of the interleukin-7-receptor alpha chain (IL7RA) in disease etiology and pathogenesis

• Applicant: Professor Dr. Roland Martin
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 102643534

The etiology of MS remains largely unknown. Current data suggest that besides the long known HLAclass II alleles the recently documented single nucleotide polymorphism (SNP)-defined haplotypes of the interleukin-7 receptor alpha chain (IL7RA) and the interleukin-2 receptor alpha chain (IL2RA) can also be considered confirmed MS-related genes. The hematopoietic growth factor cytokine interleukin- 7 (IL-7) is essential for T cell lymphogenesis in humans and promotes lymphocyte proliferation and survival. Several lines of evidence including the association of MS with certain IL7RA haplotypes, the differential expression at the transcriptional- and protein level of IL-7Rα and IL-7Rα-regulated molecules in MS patients versus controls and perturbations in thymopoiesis and peripheral T cell repertoire diversity in MS all suggest an important functional role of IL7RA in the pathogenesis of MS. Until now there are no detailed studies to analyze the functional implications of the described IL7RA MS-risk associated haplotypes. Therefore we will study T cells from patients with the MS-risk haplotype with respect to proliferation, apoptosis, IL-7-mediated signalling and IL-7Rα expression on different T cell subsets in comparison to a control group of MS patients with a defined MS-protective IL7RA haplotype or healthy controls. On the long run this could ideally lead to new therapeutic strategies targeting the IL-7/IL-7R axis.

• DFG Programme: Research Grants
• Participating Person: Dr. Sabine Rösner