Células dendríticas como determinantes del equilibrio entre inmunidad y autoinmunidad / Dendritic cells like determinants of the balance between immunity and autoimmunity

ABSTRACT

Autoinmune diseases occur when the immunological system loses its capability to recognize between self and foreign, and develops a response against healthy tissues. Both molecular bases that trigger these pathologies and genetic factors of susceptibility are unknown. Identification of these factors is fundamental for understanding and developing specific therapies for autoimmune diseases. Dendritic cells (DCs) - professional antigen presenting cells - play a fundamental roll in the development and modulation of the acquired immune response because they have the unique capacity to active naïve T lymphocytes. In order to activate T lymphocytes, the DCs must supply simultaneously two molecular signals which correspond to the antigen (or peptid complex MHC) plus costimulating signals. In absence of costimulation, the DCs induce inactivation of T lymphocytes, mechanism by which they are able to maintain peripheral tolerance against self antigens. In this way, it has been proposed that the immature DCs present antigens in absence of costimulation and provoke tolerance. On the contrary, mature DCs present antigens together with costimulating signals, which lead to immunity. In self-immune diseases, the process of tolerance in the presence of autoantigens could be deficient due to alterations in the normal function of DCs. One of the causes of this defect could be that there is an unbalance in the expression of activating and inhibiting Fcy receptors on the surface of DCs. This would generate DCs with a constitutive phenotype of maturity that would interfere with its tolerogenic activity, and would favor the permanent activation of T lymphocytes, including those that are autoreactive.