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The role of Indoleamine-2,3-dioxigenase and the Triptophan - Kynurenines axis through NMDA receptors over the immune response in the EAE and stroke model

Grant number: 11/18703-2
Support type:Research Grants - Young Investigators Grants
Duration: August 01, 2012 - July 31, 2017
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Jean Pierre Schatzmann Peron
Grantee:Jean Pierre Schatzmann Peron
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):16/21259-0 - The role of TAM receptors and their ligands, Gas6 and pros 1 during infection by Zika virus in bone marrow-derived dendritic cells and macrophages of SJL and C57BL/6 mice, BP.MS
16/07371-2 - Characterization the role of t CD8+ lymphocytes in Zika Virus infection, BP.DR
16/06096-8 - Expression and activation of TAM receptors during infection of macrophages and dendritic cells by Zika Virus, BP.IC
13/22974-7 - Modulation of the NALP3 inflamassome in microglia cells under hipóxia in vitro, BP.IC
12/10795-8 - The role of Indoleamine-2,3-dioxigenase and the tryptophan - kynurenines axis through NMDA receptors over the immune response in the EAE and stroke model, BP.JP

Abstract

It is widely known that cells from the immune system express several different receptors for neurotransmitters. Dopamine, glutamate, serotonin, P substance and VIP (Vasoactive Intestinal Peptide) are a few examples. However little is known concerning its biological functions, as it is seldom the encounter between immune cells and the brain. On the other, it has been demonstrated that in a course of central nervous system inflammation, blood-brain-barrier is disrupted and leukocytes may now enter the brain parenquima. It is then suitable that these molecules may play a relevant role over the function of such inflammatory cells. Moreover, it has been recently shown that some neurotransmitters, such as glutamate and serotonin is also produced in peripheral organs. In fact, it has already been demonstrated that dendritic cells may secrete glutamate during antigen presentation. However, the role of such molecules over lymphocytes and antigen presenting cells only elusive. At the present work we propose to study role of the tryptophan axis and its metabolites over the regulation of the immune response through NMDA receptors both in the periphery and in the central nervous system. To achieve that we will use the EAE (Experimental Autoimmune Encefalomyelitis) and the stroke models. (AU)

Scientific publications (13)
(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)
BRANDAO, WESLEY NOGUEIRA; ANDERSEN, MONICA LEVY; PALERMO-NETO, JOAO; PERON, JEAN PIERRE; ZAGER, ADRIANO. Therapeutic treatment with Modafinil decreases the severity of experimental autoimmune encephalomyelitis in mice. International Immunopharmacology, v. 75, OCT 2019. Web of Science Citations: 0.
DOS SANTOS, NILTON; NOVAES, LEONARDO S.; DRAGUNAS, GUILHERME; RODRIGUES, JENNIFER R.; BRANDAO, WESLEY; CAMARINI, ROSANA; SCHATZMANN PERON, JEAN PIERRE; DEMARCHI MUNHOZ, CAROLINA. High dose of dexamethasone protects against EAE-induced motor deficits but impairs learning/memory in C57BL/6 mice. SCIENTIFIC REPORTS, v. 9, APR 30 2019. Web of Science Citations: 1.
MESCI, PINAR; MACIA, ANGELA; LAROCK, CHRISTOPHER N.; TEJWANI, LEON; FERNANDES, ISABELLA R.; SUAREZ, NICOLE A.; ZANOTTO, PAOLO M. DE A.; BELTRAO-BRAGA, PATRICIA C. B.; NIZET, VICTOR; MUOTRI, ALYSSON R. Modeling neuro-immune interactions during Zika virus infection. Human Molecular Genetics, v. 27, n. 1, p. 41-52, JAN 1 2018. Web of Science Citations: 16.
RUSSO, FABIELE BALDINO; BALEEIRO BELTRAO-BRAGA, PATRICIA CRISTINA. The impact of Zika virus in the brain. Biochemical and Biophysical Research Communications, v. 492, n. 4, SI, p. 603-607, OCT 28 2017. Web of Science Citations: 8.
POLONIO, CAROLINA MANGANELI; DE FREITAS, CARLA LONGO; ZANLUQUI, NAGELA GHABDAN; PERON, JEAN PIERRE SCHATZMANN. Zika virus congenital syndrome: experimental models and clinical aspects. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 23, SEP 15 2017. Web of Science Citations: 5.
ROSSATO, CRISTIANO; BRANDAO, WESLEY N.; CASTRO, SANDRA B. R.; DE ALMEIDA, DANILO C.; MARANDUBA, CARLOS M. C.; CAMARA, NIELS O. S.; PERON, JEAN P. S.; SILVA, FERNANDO S. Stem cells from human-exfoliated deciduous teeth reduce tissue-infiltrating inflammatory cells improving clinical signs in experimental autoimmune encephalomyelitis. BIOLOGICALS, v. 49, p. 62-68, SEP 2017. Web of Science Citations: 6.
ABBINK, PETER; LAROCCA, RAFAEL A.; DE LA BARRERA, RAFAEL A.; BRICAULT, CHRISTINE A.; MOSELEY, EDWARD T.; BOYD, MICHAEL; KIRILOVA, MARINELA; LI, ZHENFENG; NG'ANG'A, DAVID; NANAYAKKARA, OVINI; NITYANANDAM, RAMYA; MERCADO, NOE B.; BORDUCCHI, ERICA N.; AGARWAL, ARSHI; BRINKMAN, AMANDA L.; CABRAL, CRYSTAL; CHANDRASHEKAR, ABISHEK; GIGLIO, PATRICIA B.; JETTON, DAVID; JIMENEZ, JESSICA; LEE, BENJAMIN C.; MOJTA, SHANELL; MOLLOY, KATHERINE; SHETTY, MAYURI; NEUBAUER, GEORGE H.; STEPHENSON, KATHRYN E.; PERON, JEAN PIERRE S.; ZANOTTO, PAOLO M. DE A.; MISAMORE, JOHNATHAN; FINNEYFROCK, BRAD; LEWIS, MARK G.; ALTER, GALIT; MODJARRAD, KAYVON; JARMAN, RICHARD G.; ECKELS, KENNETH H.; MICHAEL, NELSON L.; THOMAS, STEPHEN J.; BAROUCH, DAN H. Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys. Science, v. 353, n. 6304, p. 1129-1132, SEP 9 2016. Web of Science Citations: 244.
LAROCCA, RAFAEL A.; ABBINK, PETER; PERON, JEAN PIERRE S.; ZANOTTO, PAOLO M. DE A.; IAMPIETRO, M. JUSTIN; BADAMCHI-ZADEH, ALEXANDER; BOYD, MICHAEL; NG'ANG'A, DAVID; KIRILOVA, MARINELA; NITYANANDAM, RAMYA; MERCADO, NOE B.; LI, ZHENFENG; MOSELEY, EDWARD T.; BRICAULT, CHRISTINE A.; BORDUCCHI, ERICA N.; GIGLIO, PATRICIA B.; JETTON, DAVID; NEUBAUER, GEORGE; NKOLOLA, JOSEPH P.; MAXFIELD, LORI F.; DE LA BARRERA, RAFAEL A.; JARMAN, RICHARD G.; ECKELS, KENNETH H.; MICHAEL, NELSON L.; THOMAS, STEPHEN J.; BAROUCH, DAN H. Vaccine protection against Zika virus from Brazil. Nature, v. 536, n. 7617, p. 474+, AUG 25 2016. Web of Science Citations: 253.
CUGOLA, FERNANDA R.; FERNANDES, ISABELLA R.; RUSSO, FABIELE B.; FREITAS, BEATRIZ C.; DIAS, JOAO L. M.; GUIMARAES, KATIA P.; BENAZZATO, CECILIA; ALMEIDA, NATHALIA; PIGNATARI, GRACIELA C.; ROMERO, SARAH; POLONIO, CAROLINA M.; CUNHA, ISABELA; FREITAS, CARLA L.; BRANDAO, WESLEY N.; ROSSATO, CRISTIANO; ANDRADE, DAVID G.; FARIA, DANIELE DE P.; GARCEZ, ALEXANDRE T.; BUCHPIGEL, CARLOS A.; BRACONI, CARLA T.; MENDES, ERICA; SALL, AMADOU A.; ZANOTTO, PAOLO M. DE A.; PERON, JEAN PIERRE S.; MUOTRI, ALYSSON R.; BELTRAO-BRAGA, PATRICIA C. B. The Brazilian Zika virus strain causes birth defects in experimental models. Nature, v. 534, n. 7606, p. 267+, JUN 9 2016. Web of Science Citations: 539.
FOGUER, KAREN; BRAGA, MARINA DE SOUZA; SCHATZMANN PERON, JEAN PIERRE; BORTOLUCI, KARINA RAMALHO; BELLINI, MARIA HELENA. Endostatin gene therapy inhibits intratumoral macrophage M2 polarization. BIOMEDICINE & PHARMACOTHERAPY, v. 79, p. 102-111, APR 2016. Web of Science Citations: 4.
DE OLIVEIRA, DANIEL MAY; LOBATO DE OLIVEIRA, ENEDINA MARIA; RAMIRES FERRARI, MERARI DE FATIMA; SEMEDO, PATRICIA; HIYANE, MEIRE IOSHIE; CENEDEZE, MARCOS ANTONIO; PACHECO-SILVA, ALVARO; SARAIVA CAMARA, NIELS OLSEN; SCHATZMANN PERON, JEAN PIERRE. Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration. INFLAMMOPHARMACOLOGY, v. 23, n. 6, p. 343-354, DEC 2015. Web of Science Citations: 13.
SCHATZMANN PERON, JEAN PIERRE; DE BRITO, AURILEIA APARECIDA; PELATTI, MAYRA; BRANDAO, WESLEY NOGUEIRA; VITORETTI, LUANA BEATRIZ; GREIFFO, FLAVIA REGINA; DA SILVEIRA, ELAINE CRISTINA; OLIVEIRA-JUNIOR, MANUEL CARNEIRO; MALUF, MARIANGELA; EVANGELISTA, LUCILA; HALPERN, SILVIO; NISENBAUM, MARCELO GIL; PERIN, PAULO; CZERESNIA, CARLOS EDUARDO; SARAIVA CAMARA, NIELS OLSEN; AIMBIRE, FLAVIO; VIEIRA, RODOLFO DE PAULA; ZATZ, MAYANA; LIGEIRO DE OLIVEIRA, ANA PAULA. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice. PLoS One, v. 10, n. 8 AUG 31 2015. Web of Science Citations: 13.
LIGEIRO DE OLIVEIRA, ANA PAULA; SCHATZMANN PERON, JEAN PIERRE; SANTOS FRANCO, ADRIANA LINO; GOLEGA, BEATRIZ ACCETURI; VIEIRA, RODOLFO PAULA; MARTINEZ IBANEZ, OLGA CELIA; RIBEIRO, ORLANDO GARCIA; KOURY CABRERA, WAFA HANNA; DE FRANCO, MARCELO; OLIVEIRA-FILHO, RICARDO MARTINS; RIZZO, LUIZ VICENTE; VARGAFTIG, BERNARDO BORIS; DE LIMA, WOTHAN TAVARES. Ovariectomized OVA-Sensitized Mice Display Increased Frequency of CD4(+)Foxp3(+) T Regulatory Cells in the Periphery. PLoS One, v. 8, n. 6 JUN 17 2013. Web of Science Citations: 8.

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