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Disulfiram treatment suppresses antibody-producing reactions by inhibiting macrophage activation and B cell pyrimidine metabolism.
Chen, Weili; Toda, Etsuko; Takeuchi, Kazuhiro; Sawa, Yurika; Wakamatsu, Kyoko; Kuwahara, Naomi; Ishikawa, Arimi; Igarashi, Yuri; Terasaki, Mika; Kunugi, Shinobu; Terasaki, Yasuhiro; Yamada, Kazuhiko; Terashima, Yuya; Shimizu, Akira.
Afiliación
  • Chen W; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
  • Toda E; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan. t-etsuko@nms.ac.jp.
  • Takeuchi K; Laboratory for Morphological and Biomolecular Imaging, Nippon Medical School, Tokyo, Japan. t-etsuko@nms.ac.jp.
  • Sawa Y; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan. t-etsuko@nms.ac.jp.
  • Wakamatsu K; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
  • Kuwahara N; Division of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan.
  • Ishikawa A; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
  • Igarashi Y; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
  • Terasaki M; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
  • Kunugi S; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
  • Terasaki Y; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
  • Yamada K; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
  • Terashima Y; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
  • Shimizu A; Division of Pathology, Nippon Medical School Hospital, Tokyo, Japan.
Commun Biol ; 7(1): 488, 2024 Apr 22.
Article en En | MEDLINE | ID: mdl-38649462
ABSTRACT
Antibody responses, involving B cells, CD4 + T cells, and macrophages, are implicated in autoimmune diseases and organ transplant rejection. We have previously shown that inhibiting FROUNT with disulfiram (DSF) suppresses macrophage activation and migration, effectively treating inflammatory diseases. In this study, we investigated the effectiveness of DSF in antibody-producing reactions. Using a heart transplantation mouse model with antibody-mediated rejection, we administered anti-CD8 antibody to exclude cellular rejection. DSF directly inhibited B cell responses in vitro and significantly reduced plasma donor-specific antibodies and graft antibody deposition in vivo, resulting in prolonged survival of the heart graft. DSF also mediated various effects, including decreased macrophage infiltration and increased Foxp3+ regulatory T-cells in the grafts. Additionally, DSF inhibited pyrimidine metabolism-related gene expression induced by B-cell stimulation. These findings demonstrate that DSF modulates antibody production in the immune response complexity by regulating B-cell and macrophage responses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirimidinas / Linfocitos B / Disulfiram / Activación de Macrófagos Límite: Animals Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirimidinas / Linfocitos B / Disulfiram / Activación de Macrófagos Límite: Animals Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido