Therapeutic effect of the association of epicutaneous MOG and rapamycin on experimental autoimmune encephalomyelitis

Abstract

Multiple sclerosis (MS) is a progressive inflammatory disease that damages the central nervous system (CNS). Currently available therapies for MS are primarily focused in minimizing the progression of disability and reducing the number of relapses, therefore, new prophylactic and therapeutic strategies for MS are necessary. Most of the therapeutic strategies to control this disease are directed to immune modulation and inflammation control. Similar to mucosal tolerance, skin exposure to purified protein antigens may also lead to the development of immunological tolerance. Rapamycin is an antibiotic displaying antitumor and immunosuppressive activities. In this context, the present study was designed to determine if rapamycin could augment therapeutic effect of epicutaneous MOG (myelin oligodendrocyte glycoprotein) immunization on experimental autoimmune encephalomyelitis (EAE). Initially, we will determine the ideal rapamycin dose that partially reduces EAE incidence. This dose will be further used to evaluate the potential of this drug to improve MOG efficacy. Female C57BL/6 mice will be submitted to EAE induction and, 24 hours later, animals will daily receive rapamycin doses by intraperitoneal route for 10 days. MOG will be epicutaneously co-administrated on days 3 and 7 of rapamycin treatment. In both acute and chronic EAE stage, peripheral immune response and inflammatory infiltrates in the CNS will be assessed. Lastly, the immunological mechanism involved in tolerance induction will be evaluated through dendritic and regulatory T (Treg) cells phenotyping and frequency in lymphoid organs. We hypothesized that immunization with a SNC antigen delivered by an epicutaneous route in the presence of rapamycin will induce specific tolerance. Tolerogenic dendritic cells and/or Treg cells are expected to be associated with tolerance elicitation. We suppose that this tolerance will be able to protect mice from EAE development.