Abstract
BackgroundAutoimmune diseases, like multiple sclerosis, are triggered by uncontrolled activation of cells of the immune system against self-antigen present, for instance, in the central nervous system. We have reported novel biological functions for Annexin A1, an effector of endogenous anti-inflammation, to produce positive actions on the adaptive immune system by reducing the threshold of T cell activation. In this study, we investigated the potential modulatory role of Annexin A1 in the development of experimental autoimmune encephalomyelitis, a model of multiple sclerosis.MethodsMale control C57/BL6 and AnxA1 null mice were immunized subcutaneously with an emulsion consisting of 300 μg of MOG35-55 in PBS combined with an equal volume of CFA. Lymph node cells obtained from mice immunized with MOG33-55 for 14 days were re-stimulated in vitro with MOG33-55 (100 μg/ml) for 4 days and the Th1/Th17 cytokine profile measured by ELISA. Spinal cords were processed either to isolate the infiltrated T cells or fixed and stained with haematoxylin and eosin. Statistical analyses were performed using two-tailed, unpaired Student's t tests or ANOVA.ResultsOur results show a direct correlation between Annexin A1 expression and severity of EAE. Analysis of MOG35-55-induced EAE development in Annexin A1 null mice showed decreased signs of the disease compared to wild type mice. This defect was significant at the peak of the disease and accompanied by reduced infiltration of T cells in the spinal cord. Finally, analysis of the T cell recall response in vitro following stimulation with MOG35-55 showed a decrease proliferation of Annexin A1 null T cells, with a significantly reduced Th1/Th17 phenotype, compared to wild type cells.ConclusionTogether these findings suggest that Annexin A1 null mice have an impaired capacity to develop EAE. Furthermore strategies aiming at reducing Annexin A1 functions or expression in T cells might represent a novel therapeutic approach for multiple sclerosis.
Highlights
Autoimmune diseases, like multiple sclerosis, are triggered by uncontrolled activation of cells of the immune system against self-antigen present, for instance, in the central nervous system
We started off by assessing these phenomena in a mouse model of Multiple sclerosis (MS) induced by immunization with MOG35-55
We collected spinal cords and brains of wild type mice immunized with MOG35-55 peptide at different stages of the diseases i.e. at day 12, day 18 and day 20 and performed immunohystochemistry for Annexin A1 (AnxA1) side by side with hematoxylin and eosin staining
Summary
Autoimmune diseases, like multiple sclerosis, are triggered by uncontrolled activation of cells of the immune system against self-antigen present, for instance, in the central nervous system. Like many other autoimmune diseases, it is initiated by an uncontrolled T cell response to autoantigens presented in the context of MHC molecules of antigen presenting cells. In MS it is thought that myelin peptides presented by glial cells in the central nervous system (CNS) induce proliferation and activation of Th effector cells. These cells are in turn responsible for the development of the inflammatory reaction and consequent demyelination [2]
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