Prostaglandina E2 inhibts the differentiation of Th17 cells on the context of phagocytosis of infected apoptotic cells

Author(s)

Felipe Fortino Verdan da Silva

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2015-11-16

Examining board members

Alexandra Ivo de Medeiros; José Carlos Farias Alves Filho; Silvia Beatriz Boscardin; Aristóbolo Mendes da Silva; Dario Simões Zamboni

• Advisor: Alexandra Ivo de Medeiros

Abstract

The phagocytosis of apoptotic cells, also called efferocytosis, is a dynamic process critical for tissue homeostasis after injury. We and other groups previously have shown that phagocytosis of apoptotic cells promotes the synthesis of anti-inflammatory mediators such as PGE2, TGF-? and IL-10, that may result in the suppression of host defense against microorganisms. However, an elegant study using infected apoptotic cells showed that phagocytosis of these cells promote not only the generation of anti-inflammatory cytokines such as TGF-? but also IL-6 and IL-23, resulting in an immunostimulatory effect, the differentiation of Th17 cells. The role of PGE2 in adaptive immunity has been investigated regarding differentiation and activation of Th1, Th17 and Treg. Our results demonstrate that engulfment of E.coli infected apoptotic cells promotes the activation and migration of dendritic cells as well as production of pro and anti-inflammatory cytokines together with high levels of PGE2. However, differing from our hypothesis, high levels of PGE2 inhibits drastically the differentiation of Th17 cells on the context of engulfment of E.coli infected apoptotic cells by dendritic cells in vitro. The treatment of T CD4+naive cells with antagonist or agonists of EP2/EP4 receptors demonstrates the suppressor effect is mainly mediated by EP4 receptor. Finally, the instillation of E.coli infected apoptotic cells in E.coli infected animals resulted on modest Th17 increase but treatment with cox inhibitor increased Th17 cell differentiation. Therefore, our in vivo results prove the in vitro results. (AU)

• FAPESP's process: 11/20199-0 - PGE2 immunomodulatory role in Th17 differentiation during the phagocytosis of infected apoptotic cells event
• Grantee: Felipe Fortino Verdan da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate