The imbalance between Treg and Th17 cells caused by FTY720 treatment in skin allograft rejection

The imbalance between Treg and Th17 cells caused by FTY720 treatment in skin allograft rejection

Author Commodaro, Alessandra Goncalves Autor UNIFESP Google Scholar
Pedregosa, Juliana Figueredo Autor UNIFESP Google Scholar
Peron, Jean Pierre Google Scholar
Brandao, Wesley Google Scholar
Rizzo, Luiz Vicente Google Scholar
Bueno, Valquiria Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Hosp Israelita Albert Einstein
Universidade de São Paulo (USP)
Abstract OBJECTIVES: FTY720 modulates CD4(+)T cells by the augmentation of regulatory T cell activity, secretion of suppressive cytokines and suppression of IL-17 secretion by Th17 cells. To further understand the process of graft rejection/acceptance, we evaluated skin allograft survival and associated events after FTY720 treatment.METHODS: F1 mice (C57BL/6xBALB/c) and C57BL/6 mice were used as donors for and recipients of skin transplantation, respectively. the recipients were transplanted and either not treated or treated with FTY720 by gavage for 21 days to evaluate the allograft survival. in another set of experiments, the immunological evaluation was performed five days post-transplantation. the spleens, axillary lymph nodes and skin allografts of the recipient mice were harvested for phenotyping (flow cytometry), gene expression (real-time PCR) and cytokine (Bio-Plex) analysis.RESULTS: the FTY720 treatment significantly increased skin allograft survival, reduced the number of cells in the lymph nodes and decreased the percentage of Tregs at this site in the C57BL/6 recipients. Moreover, the treatment reduced the number of graft-infiltrating cells and the percentage of CD4(+) graft-infiltrating cells. the cytokine analysis (splenocytes) showed decreased levels of IL-10, IL-6 and IL-17 in the FTY720-treated mice. We also observed a decrease in the IL-10, IL-6 and IL-23 mRNA levels, as well as an increase in the IL-27 mRNA levels, in the splenocytes of the treated group. the FTY720-treated mice exhibited increased mRNA levels of IL-10, IL-27 and IL-23 in the skin graft.CONCLUSIONS: Our results demonstrated prolonged but not indefinite skin allograft survival by FTY720 treatment. This finding indicates that the drug did not prevent the imbalance between Tr1 and Th17 cells in the graft that led to rejection.
Keywords Transplantation
Rejection
Tolerance
FTY720
Foxp3
Th17
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Date 2012-01-01
Published in Clinics. São Paulo: Hospital Clinicas, Univ São Paulo, v. 67, n. 7, p. 805-813, 2012.
ISSN 1807-5932 (Sherpa/Romeo, impact factor)
Publisher Hospital Clinicas, Univ São Paulo
Extent 805-813
Origin http://dx.doi.org/10.6061/clinics/2012(07)17
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000307723100017
SciELO ID S1807-59322012000700017 (statistics in SciELO)
URI http://repositorio.unifesp.br/handle/11600/34416

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