Murine models of steroid refractory graft-versus-host disease

• Verfasst von: Toubai, Tomomi [VerfasserIn]
• Verfasst von: Rossi, Corinne [VerfasserIn]
• Titel: Murine models of steroid refractory graft-versus-host disease
• Verf.angabe: Tomomi Toubai, Corinne Rossi, Isao Tawara, Chen Liu, Cynthia Zajac, Katherine Oravecz-Wilson, Daniel Peltier, Yaping Sun, Hideaki Fujiwara, Shin-Rong Wu, Mary Riwes, Israel Henig, Stephanie Kim and Pavan Reddy
• E-Jahr: 2018
• Jahr: 20 August 2018
• Umfang: 10 S.
• Fussnoten: Gesehen am 26.04.2019
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2018
• Band/Heft Quelle: 8(2018) Article number: 12475, 10 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/s41598-018-30814-x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1663689822

Abstract

Corticosteroids are the first line therapy for acute graft-versus-host disease (GVHD). However, the outcome of steroid refractory GVHD (SR-GVHD) is poor due to a lack of effective treatments. The development of therapies for SR-GVHD is limited by an incomplete understanding of its pathophysiology partly because of the absence of clinically relevant animal models of SR-GVHD. Here we addressed the need for a SR-GVHD animal model by developing both MHC matched multiple minor histocompatibility antigens (miHAs) mismatched and MHC mismatched haploidentical murine models of SR-GVHD. We demonstrate that animals can develop SR-GVHD regardless of whether steroids are initiated early or late post allogeneic bone marrow transplantation (allo-BMT). In general, we observed increased GVHD specific histopathological damage of target organs in SR-GVHD animals relative to steroid responsive animals. Interestingly, we found no significant differences in donor T cell characteristics between steroid refractory and responsive animals suggesting that donor T cell independent mechanisms may play more prominent roles in the pathogenesis of SR-GVHD than was considered previously.