000044964 001__ 44964
000044964 005__ 20170504093353.0
000044964 0247_ $$2doi$$a10.1371/journal.pone.0124927
000044964 0248_ $$2sideral$$a93313
000044964 037__ $$aART-2015-93313
000044964 041__ $$aeng
000044964 100__ $$aVelaga, S.
000044964 245__ $$aGranzyme a is required for regulatory T-cell mediated prevention of gastrointestinal graft-versus-host disease
000044964 260__ $$c2015
000044964 5060_ $$aAccess copy available to the general public$$fUnrestricted
000044964 5203_ $$aIn our previous work we could identify defects in human regulatory T cells (Tregs) likely favoring the development of graft-versus-host disease (GvHD) following allogeneic stem cell transplantation (SCT). Treg transcriptome analyses comparing GvHD and immune tolerant patients uncovered regulated gene transcripts highly relevant for Treg cell function. Moreover, granzyme A (GZMA) also showed a significant lower expression at the protein level in Tregs of GvHD patients. GZMA induces cytolysis in a perforin-dependent, FAS-FASL independent manner and represents a cell-contact dependent mechanism for Tregs to control immune responses. We therefore analyzed the functional role of GZMA in a murine standard model for GvHD. For this purpose, adoptively transferred CD4+CD25+ Tregs from gzmA-/- mice were analyzed in comparison to their wild type counterparts for their capability to prevent murine GvHD. GzmA-/- Tregs home efficiently to secondary lymphoid organs and do not show phenotypic alterations with respect to activation and migration properties to inflammatory sites. Whereas gzmA-/- Tregs are highly suppressive in vitro, Tregs require GZMA to rescue hosts from murine GvHD, especially regarding gastrointestinal target organ damage. We herewith identify GZMA as critical effector molecule of human Treg function for gastrointestinal immune response in an experimental GvHD model.
000044964 536__ $$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/SAF2011-25390
000044964 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000044964 590__ $$a3.057$$b2015
000044964 591__ $$aMULTIDISCIPLINARY SCIENCES$$b11 / 60 = 0.183$$c2015$$dQ1$$eT1
000044964 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000044964 700__ $$aUkena, S.N.
000044964 700__ $$aDringenberg, U.
000044964 700__ $$aAlter, C.
000044964 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J.$$uUniversidad de Zaragoza
000044964 700__ $$aKershaw, O.
000044964 700__ $$aFranzke, A.
000044964 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDepartamento de Microbiología, Medicina Preventiva y Salud Pública$$cInmunología
000044964 773__ $$g10, 4 (2015), e0124927[9 pp]$$pPLoS One$$tPLoS One$$x1932-6203
000044964 8564_ $$s461651$$uhttp://zaguan.unizar.es/record/44964/files/texto_completo.pdf$$yVersión publicada
000044964 8564_ $$s104165$$uhttp://zaguan.unizar.es/record/44964/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000044964 909CO $$ooai:zaguan.unizar.es:44964$$particulos$$pdriver
000044964 951__ $$a2017-05-04-09:32:35
000044964 980__ $$aARTICLE