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

dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCOMMODARO, Alessandra Goncalves
dc.contributor.authorPEDREGOSA, Juliana Figueredo
dc.contributor.authorPERON, Jean Pierre
dc.contributor.authorBRANDAO, Wesley
dc.contributor.authorRIZZO, Luiz Vicente
dc.contributor.authorBUENO, Valquiria
dc.date.accessioned2013-07-30T15:32:32Z
dc.date.available2013-07-30T15:32:32Z
dc.date.issued2012
dc.description.abstractOBJECTIVES: 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.
dc.description.indexMEDLINE
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorshipCAPES
dc.identifier.citationCLINICS, v.67, n.7, p.805-813, 2012
dc.identifier.doi10.6061/clinics/2012(07)17
dc.identifier.issn1807-5932
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/1189
dc.language.isoeng
dc.publisherHOSPITAL CLINICAS, UNIV SAO PAULO
dc.relation.ispartofClinics
dc.rightsopenAccess
dc.rights.holderCopyright HOSPITAL CLINICAS, UNIV SAO PAULO
dc.subjectTransplantation
dc.subjectRejection
dc.subjectFTY720
dc.subjectFoxp3
dc.subjectTh17
dc.subject.othert-cells
dc.subject.othersphingosine 1-phosphate
dc.subject.otherin-vivo
dc.subject.othertransplant rejection
dc.subject.otherhelper-cells
dc.subject.othertolerance
dc.subject.othercytokines
dc.subject.otherinflammation
dc.subject.othersurvival
dc.subject.otherprotein
dc.subject.wosMedicine, General & Internal
dc.titleThe imbalance between Treg and Th17 cells caused by FTY720 treatment in skin allograft rejection
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalCOMMODARO, Alessandra Goncalves:Fed Univ Sao Paulo UNIFESP, Vis Inst, Sao Paulo, Brazil; Hosp Israelita Albert Einstein, Sao Paulo, Brazil
hcfmusp.author.externalPEDREGOSA, Juliana Figueredo:Fed Univ Sao Paulo UNIFESP, Div Nephrol, Sao Paulo, Brazil
hcfmusp.author.externalRIZZO, Luiz Vicente:Hosp Israelita Albert Einstein, Sao Paulo, Brazil
hcfmusp.citation.scopus7
hcfmusp.contributor.author-fmusphcJEAN PIERRE SCHATZMANN PERON
hcfmusp.contributor.author-fmusphcWESLEY NOGUEIRA BRANDAO
hcfmusp.contributor.author-fmusphcVALQUIRIA BUENO
hcfmusp.description.beginpage805
hcfmusp.description.endpage813
hcfmusp.description.issue7
hcfmusp.description.volume67
hcfmusp.origemWOS
hcfmusp.origem.pubmed22892927
hcfmusp.origem.scieloSCIELO:S1807-59322012000700017
hcfmusp.origem.scopus2-s2.0-84867094673
hcfmusp.origem.wosWOS:000307723100017
hcfmusp.publisher.citySAO PAULO
hcfmusp.publisher.countryBRAZIL
hcfmusp.relation.referenceAfzali B, 2007, CLIN EXP IMMUNOL, V148, P32, DOI 10.1111/j.1365-2249.2007.03356.x
hcfmusp.relation.referenceAggarwal S, 2003, J BIOL CHEM, V278, P1910, DOI 10.1074/jbc.M207577200
hcfmusp.relation.referenceBattaglia M, 2006, DIABETES, V55, P40, DOI 10.2337/diabetes.55.01.06.db05-0613
hcfmusp.relation.referenceChattopadhyay K, 2006, J IMMUNOL, V177, P3920
hcfmusp.relation.referenceChen HY, 2009, TRANSPL IMMUNOL, V21, P155, DOI 10.1016/j.trim.2009.03.006
hcfmusp.relation.referenceChen WJ, 1996, TRANSPLANTATION, V62, P705, DOI 10.1097/00007890-199609270-00001
hcfmusp.relation.referenceCommodaro AG, 2010, INVEST OPHTH VIS SCI, V51, P2568, DOI 10.1167/iovs.09-4769
hcfmusp.relation.referencede Jong E, 2010, CLIN EXP IMMUNOL, V159, P148, DOI 10.1111/j.1365-2249.2009.04041.x
hcfmusp.relation.referenceFujiwara I, 1999, TRANSPLANT P, V31, P2831, DOI 10.1016/S0041-1345(99)00582-5
hcfmusp.relation.referenceGallo AP, 2006, INT IMMUNOPHARMACOL, V6, P1919, DOI 10.1016/j.intimp.2006.07.012
hcfmusp.relation.referenceHester J, 2011, TRANSPLANTATION, V91, P744, DOI 10.1097/TP.0b013e31820c85dc
hcfmusp.relation.referenceIsoyama N, 2006, TRANSPL IMMUNOL, V15, P265, DOI 10.1016/j.trim.2006.02.004
hcfmusp.relation.referenceItoh M, 1999, J IMMUNOL, V162, P5317
hcfmusp.relation.referenceJee Y, 2007, CLIN IMMUNOL, V125, P34, DOI 10.1016/j.clim.2007.05.020
hcfmusp.relation.referenceJin JZ, 2009, TRANSPL IMMUNOL, V21, P221, DOI 10.1016/j.trim.2009.06.001
hcfmusp.relation.referenceKarim M, 2005, BLOOD, V105, P4871, DOI 10.1182/blood-2004-10-3888
hcfmusp.relation.referenceLEE RS, 1994, J EXP MED, V179, P865, DOI 10.1084/jem.179.3.865
hcfmusp.relation.referenceLi JZ, 2011, INT IMMUNOPHARMACOL, V11, P962, DOI 10.1016/j.intimp.2011.02.010
hcfmusp.relation.referenceLiao JJ, 2007, J IMMUNOL, V178, P5425
hcfmusp.relation.referenceLoong CC, 2002, J PATHOL, V197, P322, DOI 10.1002/path.1117
hcfmusp.relation.referenceLopes CT, 2010, TRANSPL P, V42, P573, DOI 10.1016/j.transproceed.2010.01.027
hcfmusp.relation.referenceLopes CT, 2008, TRANSPL P, V40, P856, DOI 10.1016/j.transproceed.2008.02.051
hcfmusp.relation.referenceMehling M, 2010, NEUROLOGY, V75, P403, DOI 10.1212/WNL.0b013e3181ebdd64
hcfmusp.relation.referenceMitchell P, 2009, CURR OPIN ORGAN TRAN, V14, P326, DOI 10.1097/MOT.0b013e32832ce88e
hcfmusp.relation.referenceOuyang WJ, 2008, IMMUNITY, V28, P454, DOI 10.1016/j.immuni.2008.03.004
hcfmusp.relation.referenceROSENBERG AS, 1988, P NATL ACAD SCI USA, V85, P7739, DOI 10.1073/pnas.85.20.7739
hcfmusp.relation.referenceSawicka E, 2005, J IMMUNOL, V175, P7973
hcfmusp.relation.referenceSayegh MH, 1998, NEW ENGL J MED, V338, P1813
hcfmusp.relation.referenceSewgobind VDKD, 2010, CLIN EXP IMMUNOL, V161, P364, DOI 10.1111/j.1365-2249.2010.04183.x
hcfmusp.relation.referenceSilva FR, 2006, INT IMMUNOPHARMACOL, V6, P1911, DOI 10.1016/j.intimp.2006.07.014
hcfmusp.relation.referenceStumhofer JS, 2006, NAT IMMUNOL, V7, P937, DOI 10.1038/ni1376
hcfmusp.relation.referenceVeldhoen M, 2006, IMMUNITY, V24, P179, DOI 10.1016/j.immuni.2006.01.001
hcfmusp.relation.referenceWalsh PT, 2004, J CLIN INVEST, V114, P1398, DOI 10.1172/JCI200423238
hcfmusp.relation.referenceWang WG, 2005, FASEB J, V19, P1731, DOI 10.1096/fj.05-3730fje
hcfmusp.relation.referenceWeaver CT, 2007, ANNU REV IMMUNOL, V25, P821, DOI 10.1146/annurev.immunol.25.022106.141557
hcfmusp.relation.referenceWolf AM, 2009, J IMMUNOL, V183, P3751, DOI 10.4049/jimmunol.0901011
hcfmusp.relation.referenceXie JH, 2003, J IMMUNOL, V170, P3662
hcfmusp.relation.referenceYoshimoto T, 2007, J IMMUNOL, V179, P4415
hcfmusp.relation.referenceZhou PJ, 2009, CLIN EXP IMMUNOL, V157, P40, DOI 10.1111/j.1365-2249.2009.03942.x
hcfmusp.remissive.sponsorshipCAPES
hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPESP
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