Project description:Lactate metabolism and signaling intricately intertwine in the context of cancer and immunity. Basigin, working alongside monocarboxylate transporters MCT1 and MCT4, orchestrates the movement of lactate across cell membranes. Despite promising potential in treating aggressive tumors, the impact of basigin antibodies on these interactions remains unclear. Our research sheds light on this complex interplay: basigin positively modulates MCT activity. A basigin antibody transforms basigin into a negative regulator of MCTs. The antibody suppresses lactate transport and enhances anti-tumor immunity in vitro and in vivo. Furthermore, antibody alters metabolic profiles in PDOs-NSCLCs and T cells. Cryo-EM structure analysis and molecular dynamics simulations unveil that MCT1’s turnover rate is influenced by the flexibility of basigin’s Ig2 domain. By restricting Ig2 flexibility, antibody reduces MCT1 turnover. These findings underscore the promise of basigin antibodies in tumor combat by influencing metabolism and immunity and the value of shared ancillary subunits in targeting heteromeric transporters.
Project description: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.
Project description:Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against SARS-CoV-2. Previous studies have shown divergent results regarding protective or damaging immunity induced by prior exposure to sCoVs. It is still unknown whether pre-existing humoral immunity may play a role in the vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera in healthy volunteers before and after immunization with inactivated SARS-CoV-2 vaccines, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level before vaccine immunization, as well as the relationship between pre-existing sCoVs immunity and vaccine-induced neutralization.
Project description:Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against SARS-CoV-2. Previous studies have shown divergent results regarding protective or damaging immunity induced by prior exposure to sCoVs. It is still unknown whether pre-existing humoral immunity may play a role in the vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera in healthy volunteers before and after immunization with inactivated SARS-CoV-2 vaccines, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level before vaccine immunization, as well as the relationship between pre-existing sCoVs immunity and vaccine-induced neutralization.
Project description:This SuperSeries is composed of the following subset Series: GSE11860: The impact of glycerol on the metabolism of Lactobacillus reuteri - Exploratory experiment GSE11861: The impact of glycerol on the metabolism of Lactobacillus reuteri - Main experiment Refer to individual Series