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

• DOI: 10.1038/s42003-024-06183-9
• Publication Date: 2024-04-22T19:01:35Z
• Authors: Weili Chen; Etsuko Toda; Kazuhiro Takeuchi; Yurika Sawa; Kyoko Wakamatsu; Naomi Kuwahara; Arimi Ishikawa; Yuri Igarashi; Mika Terasaki; Shinobu Kunugi; Yasuhiro Terasaki; Kazuhiko Yamada; Yuya Terashima; Akira Shimizu
• Keywords: Disulfiram

Abstract Antibody responses, involving B cells, CD4 + T and macrophages, are implicated in autoimmune diseases organ transplant rejection. We have previously shown that inhibiting FROUNT with disulfiram (DSF) suppresses macrophage activation migration, effectively treating inflammatory diseases. In this study, we investigated the effectiveness of DSF antibody-producing reactions. Using a heart transplantation mouse model antibody-mediated rejection, administered anti-CD8 antibody to exclude cellular directly inhibited cell responses vitro significantly reduced plasma donor-specific antibodies graft deposition vivo, resulting prolonged survival graft. also mediated various effects, including decreased infiltration increased Foxp3+ regulatory T-cells grafts. Additionally, pyrimidine metabolism-related gene expression induced by B-cell stimulation. These findings demonstrate modulates production immune response complexity regulating responses.