Murine Models of Steroid Refractory Graft-versus-Host Disease

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, Pavan Reddy

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4 Citations (Scopus)

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.

Original languageEnglish
Article number12475
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

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    Toubai, T., Rossi, C., Tawara, I., Liu, C., Zajac, C., Oravecz-Wilson, K., Peltier, D., Sun, Y., Fujiwara, H., Wu, S. R., Riwes, M., Henig, I., Kim, S., & Reddy, P. (2018). Murine Models of Steroid Refractory Graft-versus-Host Disease. Scientific reports, 8(1), [12475]. https://doi.org/10.1038/s41598-018-30814-x