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01.09.2008

Palifermin Mediates Immunoregulatory Effects in Addition to its Cytoprotective Effects in Mice with Acute Graft-Versus-Host Disease

verfasst von: Cynthia A. Ellison, Bryce M. Makar, Jacqie M. M. Wiseman, Ionela Gheorghiu, Masaru Taniguchi, John G. Gartner

Erschienen in: Journal of Clinical Immunology | Ausgabe 5/2008

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Abstract

Introduction

Treating recipient mice with palifermin (recombinant human keratinocyte growth factor) prevents the development of acute, lethal, graft-versus-host disease (GVHD). This is due, at least in part, to the ability of palifermin to protect epithelial cells from injury. Using the C57BL/6→(C57BL/6 × DBA/2)F₁-hybrid model, we previously showed that the protective effect of palifermin was also associated with redirection of the cytokine profile from Th1 to Th2.

Discussion

To study this immunoregulatory effect more directly, we induced acute GVH reactions in which we treated the donors rather than the recipients with palifermin. The recipient mice were protected from GVHD-associated morbidity, and their cytokine profile was predominantly Th2. The palifermin-treated donor mice alone showed a similar Th2 cytokine profile, and we observed elevated levels of thymic stromal lymphopoietin mRNA in the thymus. We further demonstrated that treating the donor mice with palifermin protects against GVHD-associated morbidity, even if the donors are deficient in Vα14i natural killer T cells. Our findings clearly show that palifermin mediates immunoregulatory effects in addition to its cytoprotective effects and that both are likely to be involved in the mechanism through which palifermin provides protection from acute murine GVHD.

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Titel: Palifermin Mediates Immunoregulatory Effects in Addition to its Cytoprotective Effects in Mice with Acute Graft-Versus-Host Disease
verfasst von: Cynthia A. Ellison
Bryce M. Makar
Jacqie M. M. Wiseman
Ionela Gheorghiu
Masaru Taniguchi
John G. Gartner
Publikationsdatum: 01.09.2008
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 5/2008
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-008-9216-1

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