1. Graft conditioning with fluticasone propionate reduces graft‐versus‐host disease upon allogeneic hematopoietic cell transplantation in mice
- Author
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Varady, Erika S, Ayala, L Angel, Nguyen, Pauline U, Scarfone, Vanessa M, Karimzadeh, Alborz, Zhou, Cuiwen, Chen, Xiyu, Greilach, Scott A, Walsh, Craig M, and Inlay, Matthew A
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Cancer ,Regenerative Medicine ,Stem Cell Research ,Stem Cell Research - Nonembryonic - Non-Human ,Transplantation ,Rare Diseases ,Hematology ,Stem Cell Research - Nonembryonic - Human ,Immunotherapy ,5.2 Cellular and gene therapies ,Inflammatory and immune system ,Mice ,Animals ,Fluticasone ,Transplantation ,Homologous ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Immunosuppressive Agents ,allogeneic transplantation ,blood and marrow transplantation ,glucocorticoids ,graft-versus-host disease ,hematopoietic stem cells ,Medical and Health Sciences ,Biochemistry and cell biology - Abstract
Hematopoietic cell transplantation (HCT) treats many blood conditions but remains underused due to complications such as graft-versus-host disease (GvHD). In GvHD, donor immune cells attack the patient, requiring powerful immunosuppressive drugs like glucocorticoids (GCs) to prevent death. In this study, we tested the hypothesis that donor cell conditioning with the glucocorticoid fluticasone propionate (FLU) prior to transplantation could increase hematopoietic stem cell (HSC) engraftment and reduce GvHD. Murine HSCs treated with FLU had increased HSC engraftment and reduced severity and incidence of GvHD after transplantation into allogeneic hosts. While most T cells died upon FLU treatment, donor T cells repopulated in the hosts and appeared less inflammatory and alloreactive. Regulatory T cells (Tregs) are immunomodulatory and survived FLU treatment, resulting in an increased ratio of Tregs to conventional T cells. Our results implicate an important role for Tregs in maintaining allogeneic tolerance in FLU-treated grafts and suggest a therapeutic strategy of pre-treating donor cells (and not the patients directly) with GCs to simultaneously enhance engraftment and reduce GvHD upon allogeneic HCT.
- Published
- 2023