Mast cells in the pathogenesis of experimental multiple sclerosis (English)

2012
  • Theses  /  Electronic Resource

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Mast cell (MC)-deficient c-Kit mutant KitW/W-v mice are protected against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, suggesting a detrimental role for MCs in this disease. However studies performed so far on this topic relied on a single model of MC-deficiency, the KitW/W-v, which bears several c-Kit dependent phenotypic abnormalities other than MC-deficiency, such as neutropenia and anaemia. Also, it is not clear how MCs shape the central nervous system (CNS) autoimmune response occurring in EAE. In the first work, we focused on evaluating the contribution of MCs to EAE in both KitW/W-v mice and in a newly characterized MC-deficient strain, KitW-sh/W-sh, which seems to bear fewer c-Kit dependent hematopoietic alterations. We also aimed at characterizing the T cell response to myelin antigen in a context of MC-deficiency. The comprehension of how mast cells intervene in the pathology of EAE and MS might help designing better therapies for these diseases. Histamine is one of the main preformed mediators stored in MC granules. In the second part of the thesis we evaluated the ability of histamine to modulate the response of myelin-activated T cells. We explored the effect of histamine and specific agonists of histamine receptors 1 and 2 on activation and migratory capacity of myelin-autoreactive T cells through the inflamed BBB.