Document Detail

The imbalance between Treg and Th17 cells caused by FTY720 treatment in skin allograft rejection.
MedLine Citation:
PMID:  22892927     Owner:  NLM     Status:  MEDLINE    
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.
Alessandra Gonçalves Commodaro; Juliana Figueredo Pedregosa; Jean Pierre Peron; Wesley Brandão; Luiz Vicente Rizzo; Valquiria Bueno
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinics (São Paulo, Brazil)     Volume:  67     ISSN:  1980-5322     ISO Abbreviation:  Clinics (Sao Paulo)     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-08-15     Completed Date:  2013-06-12     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101244734     Medline TA:  Clinics (Sao Paulo)     Country:  Brazil    
Other Details:
Languages:  eng     Pagination:  805-13     Citation Subset:  IM    
Vision Institute, Federal University of São Paulo, São Paulo/SP, Brazil.
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MeSH Terms
Cytokines / metabolism
Flow Cytometry
Graft Rejection / immunology,  prevention & control*
Graft Survival / drug effects*,  immunology
Immunosuppressive Agents / therapeutic use*
Interleukins / metabolism
Mice, Inbred BALB C
Mice, Inbred C57BL
Propylene Glycols / therapeutic use*
Real-Time Polymerase Chain Reaction
Skin Transplantation / immunology*
Sphingosine / analogs & derivatives*,  therapeutic use
T-Lymphocytes, Regulatory / drug effects*,  immunology
Th17 Cells / drug effects*,  immunology
Reg. No./Substance:
0/Cytokines; 0/Immunosuppressive Agents; 0/Interleukins; 0/Propylene Glycols; 123-78-4/Sphingosine; 3QN8BYN5QF/fingolimod

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