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: Cynthia A Ellison, Yuriy V Lissitsyn, Juliet A Packiasamy, Warren J Leonard, John G Gartner
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 31 Issue 3 Pg. 406-13 (Jun 2011) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 21161346 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Fibroblast Growth Factor 7
• Thymic Stromal Lymphopoietin
• TSLP protein, mouse

Topics

• Animals
• Cytokines (deficiency, genetics, metabolism)
• Disease Models, Animal
• Female
• Fibroblast Growth Factor 7 (pharmacology)
• Flow Cytometry
• Gene Deletion
• Graft vs Host Disease (immunology, physiopathology, prevention & control)
• Injections, Subcutaneous
• Lymphocyte Transfusion
• Lymphocytes (immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Knockout
• Th1-Th2 Balance (drug effects)
• Transplantation, Homologous
• Thymic Stromal Lymphopoietin