2. Academic Validation
  3. Disulfiram treatment suppresses antibody-producing reactions by inhibiting macrophage activation and B cell pyrimidine metabolism

Disulfiram treatment suppresses antibody-producing reactions by inhibiting macrophage activation and B cell pyrimidine metabolism

  • Commun Biol. 2024 Apr 22;7(1):488. doi: 10.1038/s42003-024-06183-9.
Weili Chen 1,  Etsuko Toda 2 3 4,  Kazuhiro Takeuchi 1 5,  Yurika Sawa 1,  Kyoko Wakamatsu 1,  Naomi Kuwahara 1,  Arimi Ishikawa 1,  Yuri Igarashi 1,  Mika Terasaki 1,  Shinobu Kunugi 1,  Yasuhiro Terasaki 6,  Kazuhiko Yamada 7,  Yuya Terashima 8,  Akira Shimizu 9
Affiliations

Affiliations

  • 1 Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
  • 2 Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan. t-etsuko@nms.ac.jp.
  • 3 Laboratory for Morphological and Biomolecular Imaging, Nippon Medical School, Tokyo, Japan. t-etsuko@nms.ac.jp.
  • 4 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.
  • 5 Division of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan.
  • 6 Division of Pathology, Nippon Medical School Hospital, Tokyo, Japan.
  • 7 Department of Surgery, Johns Hopkins University, Baltimore, MD, USA.
  • 8 Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
  • 9 Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan. ashimizu@nms.ac.jp.
PMID: 38649462 DOI: 10.1038/s42003-024-06183-9
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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