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The regulatory T cells and TH17 in the immune response against infections, tumors and autoimmune diseases

Grant number: 07/53940-0
Support type:Research Projects - Thematic Grants
Duration: October 01, 2007 - September 30, 2012
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:João Santana da Silva
Grantee:João Santana da Silva
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Co-Principal Investigators:Júlio César Voltarelli ; Marcos Antonio Rossi
Associated scholarship(s):09/13890-9 - Evaluation of the role of T regulator and Th17 cells during experimental infection with Toxoplasma gondii, BP.PD
08/09851-5 - The effect of statins as immune modulators during experimental Trypanosoma cruzi infection, BP.PD


This project is based on two distinct goals. One is to study the role of regulatory T cells and Th17 lymphocytes on the control of immune response. The T cells orquestrate the defense against invaders, but they can also lead to uncontrolled immune-mediated diseases. The classical Th1/Th2 axis until now has explained immunity against invaders as well as its control in order to avoid immune-mediated diseases. However, other recently described lymphocytes are involved in control or in delivery of immunity, such as, respectively, natural regulatory T (Treg) cells, and inflammatory Th17 lymphocytes. This project will study the role of Tregs and ThI7 cells in immune responses against Trypanosoma cruzi, Paracoccidiodes brasiliensis and Leishmania braziliensis, as well as their role in bacterial periodontal disease and in breast and skin (non­-melanoma) cancers and tumors or with the other side of immune responses, that is, lack of control leading to autoimmunity and tissue damage. We will determine the roles of ThI7 in tissue damage and of Treg in persistence of tumors and pathogens, as well as some of the mechanisms whereby these phenomena occur, opening new possibilities for immune interventions. The other aim is to strengthen our research group. The diversity of diseases examined in this proposal and the multidisciplinary nature of its technical and scientific approaches result in the congregation of a large group of scientists, which already interact regularly. The project works with a strong graduate program. Support from F APESP will improve the group's working conditions, therefore strengthening it and increasing the amount and quality of scientific knowledge it generates, as well as the number and quality of scientists prepared by the graduate program. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Study leads to treatment for myocarditis induced by Chagas disease 

Scientific publications (10)
(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)
COSTA, DIEGO L.; LIMA-JUNIOR, DJALMA S.; NASCIMENTO, MANUELA S.; SACRAMENTO, LAIS A.; ALMEIDA, ROQUE P.; CARREGARO, VANESSA; SILVA, JOAO S. CCR2 signaling contributes to the differentiation of protective inflammatory dendritic cells in Leishmania braziliensis infection. Journal of Leukocyte Biology, v. 100, n. 2, p. 423-432, AUG 2016. Web of Science Citations: 2.
COSTA, DIEGO L.; CARDOSO, TIAGO M.; QUEIROZ, ADRIANO; MILANEZI, CRISTIANE M.; BACELLAR, OLIVIA; CARVALHO, EDGAR M.; SILVA, JOAO S. Tr-1-Like CD4(+)CD25(-)CD127(-/low)FOXP3(-) Cells Are the Main Source of Interleukin 10 in Patients With Cutaneous Leishmaniasis Due to Leishmania braziliensis. Journal of Infectious Diseases, v. 211, n. 5, p. 708-718, MAR 1 2015. Web of Science Citations: 10.
SILVA, GRACE KELLY; COSTA, RENATA SESTI; SILVEIRA, TATIANA NUNES; CAETANO, BRAULIA COSTA; HORTA, CATARINA VELTRINI; SALAZAR GUTIERREZ, FREDY ROBERTO; DA MATTA GUEDES, PAULO MARCOS; ANDRADE, WARRISON ATHANASIO; DE NIZ, MARIANA; GAZZINELLI, RICARDO TOSTES; ZAMBONI, DARIO SIMOES; SILVA, JOAO SANTANA. Apoptosis-Associated Speck-like Protein Containing a Caspase Recruitment Domain Inflammasomes Mediate IL-1 beta Response and Host Resistance to Trypanosoma cruzi Infection. JOURNAL OF IMMUNOLOGY, v. 191, n. 6, p. 3373-3383, SEP 15 2013. Web of Science Citations: 45.
BENEVIDES, LUCIANA; CARDOSO, CRISTINA R. B.; TIEZZI, DANIEL G.; MARANA, HEITOR R. C.; ANDRADE, JURANDYR M.; SILVA, JOAO S. Enrichment of regulatory T cells in invasive breast tumor correlates with the upregulation of IL-17A expression and invasiveness of the tumor. European Journal of Immunology, v. 43, n. 6, p. 1518-1528, JUN 2013. Web of Science Citations: 52.
SILVA, GRACE K.; CUNHA, LARISSA D.; HORTA, CATARINA V.; SILVA, ALEXANDRE L. N.; GUTIERREZ, FREDY R. S.; SILVA, JOAO S.; ZAMBONI, DARIO S. A Parent-of-Origin Effect Determines the Susceptibility of a Non-Informative F1 Population to Trypanosoma cruzi Infection In Vivo. PLoS One, v. 8, n. 2 FEB 11 2013. Web of Science Citations: 10.
GUTIERREZ, FREDY R. S.; MARIANO, FLAVIA S.; OLIVEIRA, CARLO J. F.; PAVANELLI, WANDER R.; GUEDES, PAULO M. M.; SILVA, GRACE K.; CAMPANELLI, ANA P.; MILANEZI, CRISTIANE M.; AZUMA, MIYUKI; HONJO, TASUKU; TEIXEIRA, MAURO M.; ALIBERTI, JULIO C. S.; SILVA, JOAO S. Regulation of Trypanosoma cruzi-Induced Myocarditis by Programmed Death Cell Receptor. Infection and Immunity, v. 79, n. 5, p. 1873-1881, MAY 2011. Web of Science Citations: 31.
GUEDES, PAULO M. M.; OLIVEIRA, FABIANA S.; GUTIERREZ, FREDY R. S.; DA SILVA, GRACE KELLY; RODRIGUES, GERSON JHONATAN; BENDHACK, LUSIANE MARIA; FRANCO, DOUGLAS W.; DO VALLE MATTA, MARIA A.; ZAMBONI, DARIO S.; DA SILVA, ROBERTO SANTANA; SILVA, JOAO SANTANA. Nitric oxide donor trans-[RuCl([15]aneN(4))NO]2+as a possible therapeutic approach for Chagas' disease. British Journal of Pharmacology, v. 160, n. 2, p. 270-282, MAY 2010. Web of Science Citations: 41.
GARLET, GUSTAVO POMPERMAIER; GIOZZA, SILVANA PEREIRA; SILVEIRA, ELCIA MARIA; CLAUDINO, MARCELA; SANTOS, SILVANE BRAGA; AVILA-CAMPOS, MARIO JULIO; MARTINS, JR., WALTER; CARDOSO, CRISTINA RIBEIRO; FAVARO TROMBONE, ANA PAULA; CAMPANELLI, ANA PAULA; CARVALHO, EDGAR MARCELINO; SILVA, JOAEO SANTANA. Association of Human T Lymphotropic Virus 1 Amplification of Periodontitis Severity with Altered Cytokine Expression in Response to a Standard Periodontopathogen Infection. Clinical Infectious Diseases, v. 50, n. 3, p. E11-E18, FEB 1 2010. Web of Science Citations: 21.
FREDY RS GUTIERREZ; TIAGO WP MINEO; WANDER R PAVANELLI; PAULO MM GUEDES; JOÃO S SILVA. The effects of nitric oxide on the immune system during Trypanosoma cruzi infection. Memórias do Instituto Oswaldo Cruz, v. 104, p. 236-245, Jul. 2009.
GUTIERREZ, F. R. S.; GUEDES, P. M. M.; GAZZINELLI, R. T.; SILVA, J. S. The role of parasite persistence in pathogenesis of Chagas heart disease. PARASITE IMMUNOLOGY, v. 31, n. 11, p. 673-685, 2009. Web of Science Citations: 104.

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