AIRE interaction with receptors dectin-1 and dectin-2.

• Grant number: 13/00662-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2013
• End date: April 30, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Antônio Tavares de Albuquerque
• Grantee: Marco Antônio de Souza Brito
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

AIRE is a nuclear transcription factor that participates in the negative selection of lymphocytes in the thymus. Patients deficient in this protein develop a rare syndrome known as Autoimmune polyendocrinopathy-Associated Candidiasis and Ectodermal Dystrophy (APECED). This syndrome is a primary immunodeficiency characterized by the presence of various autoantibodies, hypoparathyroidism, Addison's disease and candidiasis. Although that autoimmunity can be explained by defects in the selection of self-reactive lymphocytes in the thymus, susceptibility to Candida remains unclear. Recently our group demonstrated that the AIRE protein has a cytoplasmic function which influences the recognition of compounds of the fungal cell wall-specific receptor dectin-1 and TNF-Alpha.These studies also showed that AIRE interacts with the receptor dectin-1 and with the molecules of this receptor signaling pathway including, Syk and CARD9 (Pedroza et al. J Allergy Clin Immunol, 2012). It is known that PKC signaling pathway may be modulated ´ Syk promoting the activation and regulation of the transcription factor NFkB and the production of cytokines and chemokines. This modulation may be by direct phosphorylation of PKC ´ or indirectly via phospholipase C gamma that induces the production of phosphatidylinositol generating DAG activation of PKC. Therefore, we evaluate the influence of AIRE on expression of PKC ´ and phosphorylation of phospholipase C gamma well as on the degradation of IkB and activation of NFkB p65 and c-Rel against yeast and hyphae. Thus, this study aims to contribute to the advancement of knowledge about the molecular mechanisms involved in susceptibility to candidiasis in APECED.