NF-κB inhibition in dendritic cells pre-treated with sulforaphane-conjugates induces immunotolerance

• Published in: bioRxiv
• Main Authors: Leiva-Castro, Camila, Múnera-Rodríguez, Ana M., Martínez-Bailén, Macarena, Carmona, Ana T., López-Enríquez, Soledad, Palomares, Francisca
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Laboratory 29.11.2024
• Edition: 1.1
• Subjects: Biochemistry
• ISSN: 2692-8205
• DOI: 10.1101/2024.11.27.625615

Sulforaphane (SFN) has notable health benefits but faces challenges due to poor solubility and delivery. This study explores SFN glycoconjugates’ effects on LPS-induced inflammation in human dendritic cells (DCs), aiming to enhance therapeutic potential against inflammatory diseases. Monovalent SFN-glycoconjugates with mannose (SFNMan) and fucose (SFNFuc) were developed and tested for their anti-inflammatory and immune-modulatory properties in DCs from healthy donors under chronic LPS exposure. Our results revealed that carbohydrate-functionalized SFN improves solubility and effectiveness in suppressing inflammation by targeting the p65 NF-κB pathway, without affecting MAPK signaling. SFN-glycoconjugates induce a tolerogenic immune response, characterized by increased IL-10 production and enhanced regulatory T- and B-cell proliferation. Notably, these effects surpass those of p65 NF-κB inhibition alone, highlighting a distinct and potent regulatory mechanism independent of MAPK pathways. These findings demonstrate the promise of SFN-glycoconjugates as innovative therapeutic agents for inflammatory diseases, offering enhanced anti-inflammatory and immunomodulatory effects through improved delivery and targeted molecular pathways.