Effect of efferocytosis by dendritic cells on Th17 differentiation: role of Prostaglandin E2

• Grant number: 11/17611-7
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: June 01, 2012
• End date: August 31, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandra Ivo de Medeiros
• Grantee: Alexandra Ivo de Medeiros
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 16/10964-5 - Mechanism by which PGE2 originated from efferocytosis inhibits the expression of Il-1R and Th17 differentiation - Involvement of SOCS3, BP.MS; 16/07972-6 - Evaluation of sodium chloride effect on dendritic cells maturation during efferocytosis, BP.IC; 16/01978-2 - Prostaglandin E2: receptors and signaling pathways involved in the modulation of plasticity of Th17/Th1 cells, BP.IC; + associated scholarships 15/02657-2 - Involvement of PGE2 in the modulation of IRF4 expression in Th17 cells, BP.IC; 14/24880-2 - Macrophage M1/M2 polarization throught phagocytosis of apoptotic infected cell, BP.IC; 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; 14/03967-2 - Phenotypic profile and migratory capacity of dendritic cells after apoptotic cell phagocytosis, BP.IC; 14/04961-8 - Involvement of prostaglandin E2 in Th17/Th1 cell plasticity, BP.IC; 11/20199-0 - PGE2 immunomodulatory role in Th17 differentiation during the phagocytosis of infected apoptotic cells event, BP.DR - associated scholarships

Abstract

The phagocytosis of apoptotic cells, also called efferocytosis, is a dynamic process critical for tissue homeostasis after injury. We and other groups previously shown that phagocytosis of apoptotic cells promotes the synthesis of anti-inflammatory mediators such as PGE2, TGF-beta 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 promotes the generation of anti-inflammatory cytokines such as TGF-² but also IL-6 and IL-23, resulting an immunostimulatory effect, the differentiation of Th17 cells. The role of PGE2 in adaptive immunity has been investigated as lymphocyte differentiation and activation of Th1, Th17 and Treg. Our preliminary results show that phagocytosis of infected apoptotic cells, and inflammatory cytokines also induces the production of high levels of PGE2. However, of the involvement of this lipid mediator in the context of phagocytosis of infected apoptotic cells and the mechanism by which PGE2 can 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 role of PGE2 from the efferocytosis of infected apoptotic cells in the Th17 cell differentiation. (AU)

Scientific publications

(9)

(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)

RODRIGUES, LILIAN CATALDI; SECATTO, ADRIANA; SORGI, CARLOS A.; DEJANI, NAIARA N.; MEDEIROS, ALEXANDRA I.; BORGES PRADO, MORGANA KELLY; RAMOS, SIMONE GUSMAO; CUMMINGS, RICHARD D.; STOWELL, SEAN R.; FACCIOLI, LOCIA HELENA; et al. Protective Effect of Galectin-1 during Histoplasma capsulatum Infection Is Associated with Prostaglandin E-2 and Nitric Oxide Modulation. Mediators of Inflammation, 2016. (11/17611-7, 07/02487-3, 07/00840-8)

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)

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)

CODO, ANA CAMPOS; SARAIVA, AMANDA CORREIA; DOS SANTOS, LEONARDO LIMA; VISCONDE, MARINA FRANCISCO; GALES, ANA CRISTINA; ZAMBONI, DARIO SIMOES; MEDEIROS, ALEXANDRA IVO. Inhibition of inflammasome activation by a clinical strain of Klebsiella pneumoniae impairs efferocytosis and leads to bacterial dissemination. CELL DEATH & DISEASE, v. 9, DEC 5 2018. (13/18039-0, 11/17611-7, 17/19870-6)

SALINA, ANA C. G.; SOUZA, TAIS P.; SEREZANI, CARLOS H.; MEDEIROS, ALEXANDRA I.. Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection. Innate Immunity, v. 23, n. 3, p. 219-227, APR 2017. (11/23979-7, 11/17611-7)

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)

RODRIGUES, LILIAN CATALDI; SECATTO, ADRIANA; SORGI, CARLOS A.; DEJANI, NAIARA N.; MEDEIROS, ALEXANDRA I.; BORGES PRADO, MORGANA KELLY; RAMOS, SIMONE GUSMAO; CUMMINGS, RICHARD D.; STOWELL, SEAN R.; FACCIOLI, LOCIA HELENA; et al. Protective Effect of Galectin-1 during Histoplasma capsulatum Infection Is Associated with Prostaglandin E-2 and Nitric Oxide Modulation. Mediators of Inflammation, v. 2016, p. 13-pg., 2016-01-01. (07/02487-3, 07/00840-8, 11/17611-7)