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

Hyeongjwa Choi1, Seung-Woo Yang2, Jin-Soo Joo3

  • 1Department of KONKUK-KIST Biomedical Science & Technology, Konkuk University; 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.

Clinical Immunology (Orlando, Fla.)
|December 29, 2022
PubMed

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.

Keywords:
Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrinHofbauer cellImmune toleranceInterleukin-10Preeclampsiaα-2,6-sialylated IgG

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