PGE2 immunomodulatory role in Th17 differentiation during the phagocytosis of infe...
| Grant number: | 14/03967-2 |
| Support type: | Scholarships in Brazil - Scientific Initiation |
| Effective date (Start): | April 01, 2014 |
| Effective date (End): | March 31, 2015 |
| Field of knowledge: | Biological Sciences - Immunology - Cellular Immunology |
| Principal Investigator: | Alexandra Ivo de Medeiros |
| Grantee: | Letícia de Aquino Penteado |
| Home Institution: | Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil |
| Associated research grant: | 11/17611-7 - Effect of efferocytosis by dendritic cells on Th17 differentiation: role of Prostaglandin E2, AP.JP |
Abstract Dendritic cells (DC) are professional antigen-presenting cells and one of the most able to induce the activation and differentiation of naive T cells in different lymphocyte subsets : Th1 , Th2 , Th17 and Treg. In homeostatic conditions, immature DC are as well as macrophages in the tissue represent the first line of host defense against microorganisms. During the infection, immature DC phagocyte the pathogen and acquire a mature phenotype, which promotes the migration of these cells to proximal lymphatic organs, thus promote a bridge between innate and adaptive immune responses. The change in the CD profile of immature to mature occurs through phagocytosis or interaction with pathogens via PRRs resulting in morphological change as well as the expression of chemokine receptors, MHC- II molecules and co-stimulatory molecules (CD 86 and 80) that promote the activation of T cells in the lymph node. During maturation, these DC also begin to express chemokine receptors such as CCR- 7, which allow for the recruitment of these cells to the paracortical region of lymph node. The recruitment of these CD for this region rich in T cells is controlled by CCL19 and CCL21 that are produced by stromal. Apoptosis is a physiological process during development and remodeling of tissues, and the removal of these cells by phagocytes is crucial for maintaining tolerance to self. The phagocytosis of uninfected apoptotic cells promote the production of anti- inflammatory mediators such as TGF-², IL-10 and PGE2 which promotes in vitro differentiation of T reg cells. Furthermore, the phagocytosis of infected apoptotic cells, or containing PAMPs, promotes in vitro production of mediators such as IL-23, TGF-² and IL-6 by dendritic cells. The production of these cytokines promotes the necessary condition for the generation of Th17 cells and reveals a new physiological mechanism for the generation of these cells. The hypothesis of this design is that phagocytosis of apoptotic infected and uninfected cells by dendritic cells could interfere in the maturation and migration ability of these cells to the lymph nodes as well as Th cell differentiation. | |