Murine models of steroid refractory graft-versus-host disease
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 pa...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
20 August 2018
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| In: |
Scientific reports
Year: 2018, Jahrgang: 8 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-30814-x |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1038/s41598-018-30814-x Verlag, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102256/ 
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| Verfasserangaben: | 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 |
| Zusammenfassung: | 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. |
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| Beschreibung: | Gesehen am 26.04.2019 |
| Beschreibung: | Online Resource |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-30814-x |