title: Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.
abstract: Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Japan Society for the Promotion of Science, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan; Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishiwaki
authors.affiliation: Department of Transfusion Medicine, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nishida
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Seitaro
authors.initials: S
authors.lastname: Terakura
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mizuno
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Imahashi
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan.
authors.forename: Aika
authors.initials: A
authors.lastname: Seto
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan.
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.affiliation: Department of Pathology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Takeshita
authors.affiliation: Department of Transfusion Medicine, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Shinjyuku-ku, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagao
authors.affiliation: Department of Tumor Immunology, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
chemical_list: D003907:Dexamethasone