Akt1 signaling in dendritic cells modulates host-microbe interactions and inflammatory bone resorption

• Grant number: 15/21293-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): December 20, 2015
• Effective date (End): December 19, 2016
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Carlos Rossa Junior
• Grantee: Adriana Alícia Cabrera Ortega
• Supervisor: Dana T. Graves
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Research place: University of Pennsylvania, United States
• Associated to the scholarship: 15/10100-8 - Akt1 signaling in dendritic cells modulates host-microbe interactions and inflammatory bone resorption, BP.DR

Abstract

Periodontal disease involves both the adaptive immune response and osteoclastogenesis. Dendritic cells may play a central role in the pathogenesis of periodontal disease by orchestrating the adaptive immune response and acting as osteoclast precursors. Akt signaling has an important role in processes such as metabolism, prolieration, apoptosis and immune response. Evidence indicates that Akt1 may function as an endogenous negative regulator of inflammation; however it may also enhance bone formation and inhibit osteoclastogenesis. Considering that dendritic cells are central to the immune response and are also osteoclast precursors, we propose to assess the role of Akt1 activation on inflammation and bone resorption associated with host-microbe interactions. The primary hypothesis of this proposal is that Akt1 signaling has a fundamental role for the biology of dendritic cells. Specifically, we will investigate the influence of Akt1 signaling in dendritic cells, assessing its relevance on inflammation and bone resorption. To test this primary hypothesis we propose the following specific aims:1) To determine, in vitro, the role of Akt1 signaling on the following outcomes associated with dendritic cell biology: proliferation, apoptosis, maturation/activation, migration, phagocytic activity and antigen presentation to CD4+ T cells;2) To verify the relevance of Akt1 signaling in dendritic cells in a P.gingivalis-induced experimental periodontitis model in vivo, using a cell-specific knockout approach. Outcomes assessed in this model will be: alveolar bone resorption, osteoclast number, inflammation (morphometric analysis) and homing/migration of dendritic cells to regional lymph nodes. (AU)