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IgG sialylation occurs via the FcRn-mediated recycling pathway in endothelial cells

Glendenning, L. M.; Reynero, K. M.; Kukan, E. N.; Long, M. D.; Cobb, B. A.

2023-07-02 immunology
10.1101/2023.06.30.547255 bioRxiv
Show abstract

IgG is a key mediator of immune responses throughout the human body, and the structure of the conserved glycan on the Fc region has been identified as a key inflammatory switch regulating its downstream effects. In particular, the absence of terminal sialic acid has been shown to increase the affinity of IgG for activating Fc receptors, cascading the inflammatory response in a variety of diseases and conditions. Previously, we have shown that IgG sialylation is mediated by B cell-extrinsic processes. Here, we show that the FcRn-mediated recycling pathway within endothelial cells is a critical modulator of IgG sialylation. Building a deeper understanding of how IgG sialylation is regulated will drive the development of novel therapeutics which dynamically tune IgG functionality in vivo. One-Sentence SummaryEndothelial cells remodel IgG glycans within the FcRn-mediated recycling pathway.

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