Sialylated IVIg binding to DC-SIGN+ Hofbauer cells induces immune tolerance through the caveolin-1/NF-kB pathway and IL-10 secretion

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2023-01, Vol.246, p.109215, Article 109215
• Main Authors: Choi, Hyeongjwa, Yang, Seung-Woo, Joo, Jin-Soo, Park, Min, Jin, Yihua, Kim, Ji-Woon, Lee, Seon-Yeong, Lee, Sung-Vin, Yun, Tae-Jin, Cho, Mi-La, Hwang, Han-Sung, Kang, Young-Sun
• Format: Article
• Language: English
• Subjects: Caveolin 1 - metabolism; Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin; Dendritic Cells; Female; Hofbauer cell; Humans; Immune Tolerance; Immunoglobulins, Intravenous - therapeutic use; Interleukin-10; Interleukin-10 - metabolism; Lectins, C-Type - metabolism; NF-kappa B - metabolism; Pre-Eclampsia; Preeclampsia; Pregnancy; α-2,6-sialylated IgG
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2022.109215

Although the use of IVIg has increased in various immune-driven diseases and even in pregnancy, the exact action mechanisms of IVIg are not fully understood. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) is a known receptor for α-2,6-sialylated IgG (sIVIg), which is responsible for the anti-inflammatory effect of IVIg. DC-SIGN is expressed on Hofbauer cells (HBCs) of the fetal villi of the placenta which act as an innate immune modulator at the maternal-fetal interface. Preeclampsia is a major complication in pregnancy and is related to IL-10, a cytokine with an important role in immune tolerance. DC-SIGN interaction with sIVIg in HBCs promoted IL-10 secretion through the activation of the caveolin-1/NF-κB pathway, especially in plasma lipid rafts. Consistent results were obtained for HBCs from patients with preeclampsia. Collectively, the stimulation of DC-SIGN+ HBCs with sIVIg enhanced immune tolerance in the feto-maternal environment, suggesting the therapeutic application of sIVIg to prevent preeclampsia. •Sialylated IVIg (sIVIg) binding to DC-SIGN+ Hofbauer cells in human placenta induces immune tolerable IL-10 secretion.•During this process, direct binding of caveolin-1 (Cav-1) with DC-SIGN and sequential Cav-1 phosphorylation were observed, followed by NF-κB activation.•This mechanism is firstly demonstrated in normal and critical pregnancy complication-preeclampsia (PE) placenta•These benefits of sIVIg may advance its application as a potential therapeutic strategy against various immune tolerance failures, especially pregnancy complications such as PE.