PGE2 immunomodulatory role in Th17 differentiation during the phagocytosis of infe...
| Grant number: | 14/17374-3 |
| Support type: | Scholarships abroad - Research Internship - Doctorate |
| Effective date (Start): | November 01, 2014 |
| Effective date (End): | October 31, 2015 |
| Field of knowledge: | Biological Sciences - Immunology |
| Principal Investigator: | Alexandra Ivo de Medeiros |
| Grantee: | Naiara Naiana Dejani |
| Supervisor abroad: | Carlos Henrique Serezani |
| Home Institution: | Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil |
| Local de pesquisa : | Indiana University-Purdue University Indianapolis, United States |
| Associated to the scholarship: | 12/23580-0 - Differentiation of Th17 cells during phagocytosis of infected apoptotic cells: determination of intracellular signaling pathways via PGE2 and EP receptors, BP.DR |
Abstract Phagocytosis of apoptotic cells (efferocytosis), promotes the synthesis of anti-inflammatory mediators relevant to differentiation of regulatory T cells (Treg) such as transforming growth factor (TGF-b), prostaglandin E2 (PGE2) and interleukin-10 (IL-10). However, the phagocytosis of infected apoptotic cells (infected-AC) carrying pathogen-associated molecular patterns (PAMP), elicits the synthesis of both anti- and pro-inflammatory cytokines such as TGF-b, IL-6 and IL-23 promoting Th17 cells differentiation. Our preliminary results demonstrated that phagocytosis of infected-AC promotes TGF-b and IL-6 as well as synthesis of high PGE2 levels. Moreover, unexpectedly, our results indicate that PGE2 inhibits the differentiation of Th17 cells. Among the signaling programs downstream to PGE2-EP activation, we have shown that protein kinase A activates the phosphatase and tensin homolog PTEN that further inhibits antimicrobial effector functions in macrophages. However, whether PGE2 derived from the phagocytosis of infected-AC activates PTEN that further influences Th17 commitment is unknown. The hypothesis of this project is that during T helper differentiation, in the context of infected-AC phagocytosis, PGE2 through EP4 receptor by inducing cAMP/PKA/Epac signaling promotes PTEN activation and inhibits the activation of transcription factors, such as STAT3 that is required for Th17 differentiation. Because Th17 is implicated in the pathogenesis of inflammation and autoimmune diseases this study might lead to improved understanding of the crucial signaling mechanisms and pathways by which PGE2 inhibits Th17 differentiation and may have important clinical implications in the future. (AU) | |
| Articles published in Agência FAPESP about the scholarship:Defesa do organismo em infecção intestinal é ditada por mediador lipídico Defense against intestinal infection in organism is affected by prostaglandin E<sub>2</sub> | |