title: Role of thymic stromal lymphopoietin (TSLP) in palifermin-mediated immune modulation and protection from acute murine graft-versus-host disease.
abstract: Using the C57BL/6→(C57BL/6 x DBA/2)F(1)-hybrid model of acute graft-versus-host disease (GVHD), we previously showed that treating the donor mice with palifermin provides protection from morbidity and a shift from Th1 to Th2 cytokine production. To determine whether thymic stromal lymphopoietin (TSLP) is involved in palifermin-mediated immune modulation, we used donors from the following groups: (1) untreated wild-type donors, (2) palifermin-treated wild-type donors, (3) untreated TSLPR(-/-) donors, and (4) palifermin-treated TSLPR(-/-) donors. Survival in the recipients was 0%, 100%, 31%, and 0%, for groups 1-4, respectively, indicating that TSLP responsiveness is required for palifermin-mediated protection from GVHD. We also found that the increases in Th2 cytokine levels that are induced by palifermin treatment are obviated in TSLPR(-/-) donors, and that protection from GVHD (group 2) is associated with a higher percentage of CD4(+)CD25(+)Foxp3(+) cells in the graft. Collectively, our findings show that when palifermin and TSLP act in concert, the predominant effect is protection in this model.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Manitoba, 401 Brodie Center, 727 McDermot Avenue, Winnipeg, MB, Canada. ellisonc@ms.umanitoba.ca
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Ellison
authors.forename: Yuriy V
authors.initials: YV
authors.lastname: Lissitsyn
authors.forename: Juliet A
authors.initials: JA
authors.lastname: Packiasamy
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
authors.forename: John G
authors.initials: JG
authors.lastname: Gartner
mesh_terms: D000818:Animals; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology; D005434:Flow Cytometry; D017353:Gene Deletion; D006086:Graft vs Host Disease / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control; D007279:Injections, Subcutaneous; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D058408:Th1-Th2 Balance / Q000187:drug effects*; D014184:Transplantation, Homologous; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D051523:Fibroblast Growth Factor 7; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse