Modulation of experimental autoimmune encephalomyelitis by endogenous Annexin A1
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 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.
Methods: Male control C57/BL6 and AnxA1 null mice were immunized subcutaneously with an emulsion consisting of 300 g 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 g/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.
Results: Our results show a direct correlation between Annexin A1 expression and severity ofEAE.
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.
Conclusions: Together 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.
Published on: 2009-11-13