Tese de mestrado, Biologia (Biologia Molecular e Genética), 2008, Universidade de Lisboa, Faculdade de CiênciasMultiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system (CNS). It is estimated that over 2.5 million people, mainly young adults between 25 and 40 years old, suffer from this disease. MS pathology is characterized by multifocal CNS inflammation, degeneration of the myelin sheath, surrounding the axons of neurons, and formation of sclerotic plaques that leads to axonal damage. The etiology of the disease remains unknown with genetic and environmental factors being important for its development. Mechanisms that lead to CNS degeneration result from a local inflammatory response characterized by the recruitment of T cells that recognize myelin peptides against which they mount an effector response. Heme Oxygenase-1 (HO-1) is a ubiquitously expressed stress-induced enzyme, responsible for the degradation of free heme into iron (Fe), biliverdin (BV) and carbon monoxide (CO). HO-1 controls inflammatory processes such as the ones associated with the development of MS. It is expressed in the CNS during MS as well as in experimental autoimmune encephalomyelitis (EAE), a murine model of MS. Deletion of HO-1 is associated with increased susceptibility to EAE, while pharmacological induction of its expression arrests EAE progression. The protective effect of HO-1 is associated with inhibition of expression of histocompatibility complex class II (MHC class II) on antigen presenting cells (APC), including dendritic cells (DCs). The main hypothesis tested in this project was that expression of HO-1 in DCs might modulate T cell responses in a manner that prevents the progression of EAE. We found that absence of HO-1 in DCs does not affect significantly its maturation by modulating the expression of surface activation markers. However, we failed to demonstrate whether this absence could afford any effect on the disease, when DCs are adoptively transferred into naïve mice, leading to a more severe outcome when compared to Hmox1+/+ DCsResumo alargado em português disponível no document
