IL-7Rα 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 alpha (IL-7Rα) as a risk factor for multiple sclerosis. But the role of IL-7Rα in experimental autoimmune encephalomyelitis (EAE) model of MS is not known. In this study we demonstrate that IL-7Rα deficient (IL-7Rα−/−) mice remain resistant to MOGp35-55-induced EAE. When compared to C57BL/6 wild type mice, IL-7Rα−/− mice showed less severe inflammation and demyelination in the CNS. The attenuation of EAE in IL-7Rα−/− mice was associated with a decrease in T helper (Th) 1 and Th17 responses in the CNS and lymphoid organs. IL-7Rα−/− mice also showed an increase in Th2 response and CD4+Foxp3+ regulatory T cells. These findings highlight that IL-7Rα confers susceptibility by influencing autoimmune Th1/Th17 responses in EAE model of MS.

Blockade of CD127 Exerts a Dichotomous Clinical Effect in Marmoset Experimental Autoimmune Encephalomyelitis

“…Represented are cells within the live lymphocyte population. Statistical significance (P<0.05) is indicated by an asterisk prophylactically with anti-IL-7Rα neutralizing mAb mitigates EAE severity via partial depletion of naïve and effector memory CD4 and CD8 T cell subsets (Ashbaugh et al 2013;Lee et al 2011;Walline et al 2011). Although deficiencies in IL-7R alter both Th1 and Th17 populations, work by Lee et al strongly supports the notion that IL-7 plays a role in the development of pathogenic Th1 cells, but not the Th17 cell (Lee et al 2011).…”

“…The IL-7 signaling pathway has raised much interest as target of immunotherapy in human autoimmune disease. Recent findings showed that blockade or deletion of the IL-7 receptor ameliorates T-cell-mediated autoimmune disease, such as in C57BL/6 and SJL/J mice models of experimental autoimmune encephalomyelitis (EAE); the animal model for MS (Ashbaugh et al 2013;Lee et al 2011;Walline et al 2011).…”

Increased (6 exon) interleukin-7 production after M. tuberculosis infection and soluble interleukin-7 receptor expression in lung tissue

“…40 In addition, IL-7 has been shown to expand antigen-specific IL-17-producing T cells in a murine experimental autoimmune encephalomyelitis model. 41 We show in the current report detection of increased IL-17 production in rBCG-vaccinated NHPs when compared with BCG-vaccinated or control animals. IL-17 has been shown to confer protection against Mtb in murine model.…”

Th17 cells in systemic lupus erythematosus share functional features with Th17 cells from normal bone marrow and peripheral tissues

“…This close relationship between Th1 and Th17 cells is also marked in their capacity to cause T-cell-mediated inflammation and autoimmune disease. In fact, Th17 cells have been found to have a pathogenic role in several autoimmune disorders, including experimental autoimmune encephalomyelitis [8], rheumatoid arthritis [9,10], inflammatory bowel disease [11], systemic sclerosis [12] and systemic lupus erythematosus (SLE) [13,14], which were previously thought to be mainly caused by Th1 responses. Interestingly, new studies show Th17 cells as more potent than Th1 cells in inducing disease [15], linking the cytokine IL-17 in coordinating tissue inflammation via the up-regulation of additional proinflammatory and neutrophil-recruiting cytokines and chemokines, suggesting a pro-inflammatory role in these conditions.…”