Graft conditioning with fluticasone propionate reduces graft-versus-host disease upon allogeneic hematopoietic cell transplantation in mice.

Autor: Varady ES; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA., Ayala LA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA., Nguyen PU; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA., Scarfone VM; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA., Karimzadeh A; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA., Zhou C; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA., Chen X; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA., Greilach SA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA., Walsh CM; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA., Inlay MA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2023 Sep 11; Vol. 15 (9), pp. e17748. Date of Electronic Publication: 2023 Aug 04.
DOI: 10.15252/emmm.202317748
Abstrakt: 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.
(© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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