Differentiation of Th17 cells during phagocytosis of infected apoptotic cells: Determination of intracellular signaling pathways via PGE2 and EP receptors

• Grant number: 12/23580-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2014
• End date: July 31, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandra Ivo de Medeiros
• Grantee: Naiara Naiana Dejani
• Host 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
• Associated scholarship(s): 14/17374-3 - Studying the role of PGE2/EP4/PTEN axis in Th17 differentiation during phagocytosis of infected apoptotic cells, BE.EP.DR

Abstract

The phagocytosis of apoptotic cells, also called efferocytosis, promotes the synthesis of anti-inflammatory mediators such as transforming growth factor (TGF-²), prostaglandin E2 (PGE2) and interleukin-10 (IL-10), relevant to differentiation of regulatory T cells (Treg). However, the phagocytosis of infected apoptotic cells carrying pathogen-associated molecular patterns - PAMP, directs the simultaneous synthesis of anti and pro-inflammatory cytokines such as TGF-², IL-6 and IL-23, these favor the induction of helper T 17 cells (Th17). Preliminary results obtained recently by our group demonstrated that phagocytosis of infected apoptotic cells promotes both TGF-² and IL-6 as the synthesis of high PGE2 levels. The importance of PGE2 in adaptive immunity, differentiation and activation of Th1, Th17 and Treg has been the subject of study in different experimental models. However, the role of PGE2, derived from the phagocytosis of infected apoptotic cells, in the differentiation of Th17 cells and the intracellular mechanisms by which this lipid mediator could work synergistically with TGF-², IL-6 and IL-23 in the process of Th17 cell differentiation is unknown. The hypothesis of this project is to study the signaling mechanisms by which PGE2, via receptors (EP), promotes the differentiation of Th17 cells in the context of phagocytosis of infected apoptotic cells.

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DEJANI, NAIARA N.; BRANDT, STEPHANIE L.; PINEROS, ANNIE; GLOSSON-BYERS, NICOLE L.; WANG, SUE; SON, YOUNG MIN; MEDEIROS, ALEXANDRA I.; SEREZANI, C. HENRIQUE. Topical Prostaglandin E Analog Restores Defective Dendritic Cell-Mediated Th17 Host Defense Against Methicillin-Resistant Staphylococcus Aureus in the Skin of Diabetic Mice. Diabetes, v. 65, n. 12, p. 3718-3729, DEC 2016. (11/17611-7, 14/17374-3, 12/23580-0)

LOPES, DEBORA E. M.; JABR, CAMILA L.; DEJANI, NAIARA N.; SARAIVA, AMANDA C.; DE AQUINO, SABRINA G.; MEDEIROS, ALEXANDRA I.; ROSSA JUNIOR, CARLOS. Inhibition of 5-lipoxygenase attenuates inflammation and bone resorption in lipopolysaccharide-induced periodontal disease. Journal of Periodontology, v. 89, n. 2, p. 235-245, FEB 2018. (11/17611-7, 12/23580-0)

DEJANI, NAIARA NAIANA; ORLANDO, ALLAN BOTINHON; NINO, VICTORIA EUGENIA; PENTEADO, LETICIA DE AQUINO; VERDAN, FELIPE FORTINO; RIBEIRO BAZZANO, JULIA MIRANDA; CODO, ANA CAMPOS; GUERTA SALINA, ANA CAROLINA; SARAIVA, AMANDA CORREIA; AVELAR, MATHEUS ROSSI; et al. Intestinal host defense outcome is dictated by PGE(2) production during efferocytosis of infected cells. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 115, n. 36, p. E8469-E8478, SEP 4 2018. (16/10964-5, 11/17611-7, 12/23580-0, 14/03967-2)

PENTEADO, LETICIA DE AQUINO; DEJANI, NAIARA NAIANA; VERDAN, FELIPE FORTINO; ORLANDO, ALLAN BOTINHON; NINO, VICTORIA EUGENIA; DIAS, FERNANDA DE NUZZI; GUERTA SALINA, ANA CAROLINA; MEDEIROS, ALEXANDRA IVO. Distinctive role of efferocytosis in dendritic cell maturation and migration in sterile or infectious conditions. IMMUNOLOGY, v. 151, n. 3, p. 304-313, JUL 2017. (16/10964-5, 11/17611-7, 12/23580-0, 14/03967-2)

SALINA, ANA CAROLINA GUERTA; PENTEADO, LETICIA DE AQUINO; DEJANI, NAIARA NAIANA; SILVA-PEREIRA, LUDMILLA; RAIMUNDO, BRENO VILAS BOAS; CORREA, GABRIEL FERRANTI; OLIVEIRA, KAREN CRISTINA; RAMALHO, LEANDRA NAIRA ZAMBELLI; BOKO, MEDETON MAHOUSSI MICHAEL; BONATO, VANIA L. D.; et al. Different bacterial cargo in apoptotic cells drive distinct macrophage phenotypes. Apoptosis, v. N/A, p. 10-pg., 2023-10-05. (11/17611-7, 12/23580-0, 20/09327-6, 17/21629-5, 16/10964-5, 18/19638-9, 17/04786-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

DEJANI, Naiara Naiana. Prostaglandin E2 via EP4/IL-1R inhibits Th17 cell differentiation during the efferocytosis of infected cells. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.