Dataset Information

IL-7R? confers susceptibility to experimental autoimmune encephalomyelitis.

ABSTRACT: Multiple sclerosis (MS) is a neurological disorder that causes paralysis in young adults and affects women more frequently than men. The etiology of MS is not known, but it is generally viewed as an autoimmune disease of the central nervous system (CNS), influenced by genetic and environmental factors. Recent studies have identified interleukin-7 receptor ? (IL-7R?) as a risk factor for MS. But the role of IL-7R? in experimental autoimmune encephalomyelitis (EAE) model of MS is not known. In this study we demonstrate that IL-7R?-deficient (IL-7R?(-/-)) mice remain resistant to MOGp35-55-induced EAE. When compared with C57BL/6 wild-type mice, IL-7R?(-/-) mice showed less severe inflammation and demyelination in the CNS. The attenuation of EAE in IL-7R?(-/-) mice was associated with a decrease in T-helper (Th) 1 and Th17 responses in the CNS and lymphoid organs. IL-7R?(-/-) mice also showed an increase in Th2 response and CD4(+)Foxp3(+) regulatory T cells. These findings highlight that IL-7R? confers susceptibility by influencing autoimmune Th1/Th17 responses in EAE model of MS.

SUBMITTER: Walline CC

PROVIDER: S-EPMC3024464 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IL-7Rα confers susceptibility to experimental autoimmune encephalomyelitis.

Walline C C CC Kanakasabai S S Bright J J JJ

Genes and immunity 20100923 1

Multiple sclerosis (MS) is a neurological disorder that causes paralysis in young adults and affects women more frequently than men. The etiology of MS is not known, but it is generally viewed as an autoimmune disease of the central nervous system (CNS), influenced by genetic and environmental factors. Recent studies have identified interleukin-7 receptor α (IL-7Rα) as a risk factor for MS. But the role of IL-7Rα in experimental autoimmune encephalomyelitis (EAE) model of MS is not known. In thi ...[more]

PMID: 20861865

Similar Datasets

Project description:Background: Interleukin 37 (IL-37), a member of IL-1 family, broadly suppresses inflammation in many pathological conditions by acting as a dual-function cytokine in that IL-37 signals via the extracellular receptor complex IL1-R5/IL-1R8, but it can also translocate to the nucleus. However, whether IL-37 exerts beneficial actions in neuroinflammatory diseases, such as multiple sclerosis, remains to be elucidated. Thus, the goals of the present study were to evaluate the therapeutic effects of IL-37 in a mouse model of multiple sclerosis, and if so, whether this is mediated via the extracellular receptor complex IL-1R5/IL-1R8. Methods: We used a murine model of MS, the experimental autoimmune encephalomyelitis (EAE). We induced EAE in three different single and double transgenic mice (hIL-37tg, IL-1R8 KO, hIL-37tg-IL-1R8 KO) and wild type littermates. We also induced EAE in C57Bl/6 mice and treated them with various forms of recombinant human IL-37 protein. Functional and histological techniques were used to assess locomotor deficits and demyelination. Luminex and flow cytometry analysis were done to assess the protein levels of pro-inflammatory cytokines and different immune cell populations, respectively. qPCRs were done to assess the expression of IL-37, IL-1R5 and IL-1R8 in the spinal cord of EAE, and in blood peripheral mononuclear cells and brain tissue samples of MS patients. Results: We demonstrate that IL-37 reduces inflammation and protects against neurological deficits and myelin loss in EAE mice by acting via IL1-R5/IL1-R8. We also reveal that administration of recombinant human IL-37 exerts therapeutic actions in EAE mice. We finally show that IL-37 transcripts are not up-regulated in peripheral blood mononuclear cells and in brain lesions of MS patients, despite the IL-1R5/IL-1R8 receptor complex is expressed. Conclusions: This study presents novel data indicating that IL-37 exerts therapeutic effects in EAE by acting through the extracellular receptor complex IL-1R5/IL-1R8, and that this protective physiological mechanism is defective in MS individuals. IL-37 may therefore represent a novel therapeutic avenue for the treatment of MS with great promising potential.

Dataset Information

IL-7R? confers susceptibility to experimental autoimmune encephalomyelitis.

Publications

IL-7Rα confers susceptibility to experimental autoimmune encephalomyelitis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets