Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease

Kaori Sato, Kawori Eizumi, Tomohiro Fukaya, Shigeharu Fujita, Yumiko Sato, Hideaki Takagi, Mai Yamamoto, Naohide Yamashita, Atsushi Hijikata, Hiroshi Kitamura, Osamu Ohara, Sho Yamasaki, Takashi Saito, Katsuaki Sato

    Research output: Contribution to journalArticle

    34 Citations (Scopus)

    Abstract

    Chronic graft-versus-host disease (cGVHD) is a limiting factor in allogeneic hematopoietic stem cell transplantation (alloHSCT) for the treatment of leukemia and other malignancies. Relative to the process that initiates and promotes cGVHD, the regulation is poorly understood. In this study, we examined the role of naturally occurring regulatory dendritic cells (DC regs ) in murine major histocompatibility complex (MHC)-compatible and multiple minor histocompatibility antigen (miHAg)-incompatible model of cGVHD in alloHSCT. DC regs generated from bone marrow in vitro (BM-DC regs ) exclusively expressed CD200 receptor 3 (CD200R3), which exerted a suppressive function in the Ag-specific CD4 + T-cell response. CD49 + CD200R3 + cells showed similarities in phenotype and function to BM-DC regs , which formally distinguishes them from other leukocytes, suggesting that they are the natural counterpart of BM-DC regs . Treatment of the recipient mice after alloHSCT with the recipient-type CD49 + CD200R3 + cells as well as BM-D Cregs protected against cGVHD, and the protection was associated with the generation of Ag-specific anergic CD4 + T cells as well as CD4 + CD25 + Foxp3 + regulatory T cells (T regs ) from donor-derived alloreactive CD4 + CD25 - Foxp3 - T cells. In addition, the depletion of CD49 + CD200R3 + cells before alloHSCT enhanced the progression of cGVHD. In conclusion, CD49 + CD200R3 + cells act as naturally occurring D Cregs to regulate the pathogenesis of cGVHD in alloHSCT mediated through the control of the transplanted alloreactive CD4 + T cells.

    Original languageEnglish
    Pages (from-to)4780-4789
    Number of pages10
    JournalBlood
    Volume113
    Issue number19
    DOIs
    Publication statusPublished - Nov 17 2009

    Fingerprint

    Graft vs Host Disease
    T-cells
    Grafts
    Hematopoietic Stem Cell Transplantation
    Dendritic Cells
    Stem cells
    Skin
    T-Lymphocytes
    Minor Histocompatibility Antigens
    Regulatory T-Lymphocytes
    Major Histocompatibility Complex
    Bone
    Leukemia
    Leukocytes
    Bone Marrow
    Phenotype
    Therapeutics
    Neoplasms

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

    Cite this

    Sato, K., Eizumi, K., Fukaya, T., Fujita, S., Sato, Y., Takagi, H., ... Sato, K. (2009). Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease. Blood, 113(19), 4780-4789. https://doi.org/10.1182/blood-2008-10-183145

    Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease. / Sato, Kaori; Eizumi, Kawori; Fukaya, Tomohiro; Fujita, Shigeharu; Sato, Yumiko; Takagi, Hideaki; Yamamoto, Mai; Yamashita, Naohide; Hijikata, Atsushi; Kitamura, Hiroshi; Ohara, Osamu; Yamasaki, Sho; Saito, Takashi; Sato, Katsuaki.

    In: Blood, Vol. 113, No. 19, 17.11.2009, p. 4780-4789.

    Research output: Contribution to journalArticle

    Sato, K, Eizumi, K, Fukaya, T, Fujita, S, Sato, Y, Takagi, H, Yamamoto, M, Yamashita, N, Hijikata, A, Kitamura, H, Ohara, O, Yamasaki, S, Saito, T & Sato, K 2009, 'Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease', Blood, vol. 113, no. 19, pp. 4780-4789. https://doi.org/10.1182/blood-2008-10-183145
    Sato, Kaori ; Eizumi, Kawori ; Fukaya, Tomohiro ; Fujita, Shigeharu ; Sato, Yumiko ; Takagi, Hideaki ; Yamamoto, Mai ; Yamashita, Naohide ; Hijikata, Atsushi ; Kitamura, Hiroshi ; Ohara, Osamu ; Yamasaki, Sho ; Saito, Takashi ; Sato, Katsuaki. / Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease. In: Blood. 2009 ; Vol. 113, No. 19. pp. 4780-4789.
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    abstract = "Chronic graft-versus-host disease (cGVHD) is a limiting factor in allogeneic hematopoietic stem cell transplantation (alloHSCT) for the treatment of leukemia and other malignancies. Relative to the process that initiates and promotes cGVHD, the regulation is poorly understood. In this study, we examined the role of naturally occurring regulatory dendritic cells (DC regs ) in murine major histocompatibility complex (MHC)-compatible and multiple minor histocompatibility antigen (miHAg)-incompatible model of cGVHD in alloHSCT. DC regs generated from bone marrow in vitro (BM-DC regs ) exclusively expressed CD200 receptor 3 (CD200R3), which exerted a suppressive function in the Ag-specific CD4 + T-cell response. CD49 + CD200R3 + cells showed similarities in phenotype and function to BM-DC regs , which formally distinguishes them from other leukocytes, suggesting that they are the natural counterpart of BM-DC regs . Treatment of the recipient mice after alloHSCT with the recipient-type CD49 + CD200R3 + cells as well as BM-D Cregs protected against cGVHD, and the protection was associated with the generation of Ag-specific anergic CD4 + T cells as well as CD4 + CD25 + Foxp3 + regulatory T cells (T regs ) from donor-derived alloreactive CD4 + CD25 - Foxp3 - T cells. In addition, the depletion of CD49 + CD200R3 + cells before alloHSCT enhanced the progression of cGVHD. In conclusion, CD49 + CD200R3 + cells act as naturally occurring D Cregs to regulate the pathogenesis of cGVHD in alloHSCT mediated through the control of the transplanted alloreactive CD4 + T cells.",
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    AU - Sato, Yumiko

    AU - Takagi, Hideaki

    AU - Yamamoto, Mai

    AU - Yamashita, Naohide

    AU - Hijikata, Atsushi

    AU - Kitamura, Hiroshi

    AU - Ohara, Osamu

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