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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\u2010treated grafts and suggest a therapeutic strategy of pre\u2010treating donor cells (and not the patients directly) with GCs to simultaneously enhance engraftment and reduce GvHD upon allogeneic HCT.<\/jats:p>","DOI":"10.15252\/emmm.202317748","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T03:35:25Z","timestamp":1691120125000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Graft conditioning with fluticasone propionate reduces graft\u2010versus\u2010host disease upon allogeneic hematopoietic cell transplantation in mice"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8125-0033","authenticated-orcid":false,"given":"Erika S","family":"Varady","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6272-3314","authenticated-orcid":false,"given":"L Angel","family":"Ayala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline U","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa M","family":"Scarfone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alborz","family":"Karimzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiwen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6314-5468","authenticated-orcid":false,"given":"Xiyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A","family":"Greilach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7808-2817","authenticated-orcid":false,"given":"Craig M","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-2076","authenticated-orcid":false,"given":"Matthew A","family":"Inlay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"BFEMMM202317748_CR1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.4049\/jimmunol.136.2.389","volume":"136","author":"JD Ashwell","year":"1986","unstructured":"Ashwell JD, Chen C, Schwartz RH (1986) High frequency and nonrandom distribution of alloreactivity in T cell clones selected for recognition of foreign antigen in association with self class II molecules. 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