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The role of Th17 and t regulatory (Tregs) cells in the immunomodulation of experimental periapial lesions

Grant number: 12/15133-3
Support type:Regular Research Grants
Duration: March 01, 2013 - February 28, 2015
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Gustavo Pompermaier Garlet
Grantee:Gustavo Pompermaier Garlet
Home Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

The establishment, progression and outcome of chronic periapical lesions, albeit dependent on the presence of pathogenic microorganisms, are highly dependent of the nature of host inflammatory immune response in periapical environment. In this scenario, distinct subsets of lymphocytes and its prototypical cytokines have been implicated in such lesions pathogenesis, being recently Th17 and Regulatory (Tregs) cells alleged as potential determinants of lesions severity. However, such associations are still elusive, being not confirmed by clear cause-effect studies, being the role of Th17 and Tregs in periapical lesions pathogenesis still unknown, as well the potential mechanisms by which such cells can modulate lesions outcome. Therefore, we propose the investigation of the role of Tregs and Th17 cells in the immunopathogenesis of experimental periapical lesions using a mouse model (Fukada, Silva et al. 2008; Garlet, Fukada et al. 2010), by means of the characterization of the histomorphometric and molecular features of lesions induced in C57Bl/6 (WT) mice treated with anti-GITR antibody (which inhibits Tregs by the interaction with CITR receptor)(Garlet et al 2010), and the use of IL-17KO strain, when compared with control untreated WT mice. The endpoints for lesions analysis will be the histopathological and histomorphometric features of periapical lesions, the staining and counting of osteoclasts in the lesions, and the analysis of mRNA (RealTimePCRarray) and protein (ELISA multiplex) profile at response site being inflammatory immune response factors as primary targets, as well mediators of soft tissue destruction and osteoclastogenic factors. The overall comparative analysis will allow the determination of the roles of Tregs and Th17 cells in the development of periapical diseases, and of the mechanisms involved in its regulation, which will certainly contribute the development of new diagnostic and therapeutic strategies to the management of such pathologies. (AU)

Scientific publications (4)
(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)
FRANCISCONI, C. F.; VIEIRA, A. E.; AZEVEDO, M. C. S.; TABANEZ, A. P.; FONSECA, A. C.; TROMBONE, A. P. F.; LETRA, A.; SILVA, R. M.; SFEIR, C. S.; LITTLE, S. R.; GARLET, G. P. RANKL Triggers Treg-Mediated Immunoregulation in Inflammatory Osteolysis. JOURNAL OF DENTAL RESEARCH, v. 97, n. 8, p. 917-927, JUL 2018. Web of Science Citations: 6.
FRANCISCONI, CAROLINA FAVARO; VIEIRA, ANDREIA ESPINDOLA; BIGUETTI, CLAUDIA CRISTINA; GLOWACKI, ANDREW J.; FAVARO TROMBONE, ANA PAULA; LETRA, ARIADNE; SILVA, RENATO MENEZES; SFEIR, CHARLES S.; LITTLE, STEVEN R.; GARLET, GUSTAVO POMPERMAIER. Characterization of the Protective Role of Regulatory T Cells in Experimental Periapical Lesion Development and Their Chemoattraction Manipulation as a Therapeutic Tool. JOURNAL OF ENDODONTICS, v. 42, n. 1, p. 120-126, JAN 2016. Web of Science Citations: 14.
ARAUJO-PIRES, ANA CLAUDIA; BIGUETTI, CLAUDIA CRISTINA; REPEKE, CARLOS EDUARDO; RODINI, CAMILA DE OLIVEIRA; CAMPANELLI, ANA PAULA; FAVARO TROMBONE, ANA PAULA; LETRA, ARIADNE; SILVA, RENATO MENEZES; GARLET, GUSTAVO POMPERMAIER. Mesenchymal Stem Cells as Active Prohealing and Immunosuppressive Agents in Periapical Environment: Evidence from Human and Experimental Periapical Lesions. JOURNAL OF ENDODONTICS, v. 40, n. 10, p. 1560-1565, OCT 2014. Web of Science Citations: 16.
ARAUJO-PIRES, ANA CLAUDIA; FRANCISCONI, CAROLINA FAVARO; BIGUETTI, CLAUDIA CRISTINA; CAVALLA, FRANCO; FABIO ARANHA, ANDREZA MARIA; LETRA, ARIADNE; FAVARO TROMBONE, ANA PAULA; FAVERI, MARCELO; SILVA, RENATO MENEZES; GARLET, GUSTAVO POMPERMAIER. Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status. Journal of Applied Oral Science, v. 22, n. 4, p. 336-346, Jul. 2014. Web of Science Citations: 49.

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