MZB1 enables efficient interferon α secretion in stimulated plasmacytoid 
dendritic cells

Kapoor, Tanya; Corrado, Mauro; Pearce, Erika L.; Pearce, Edward J.; Grosschedl, Rudolf

doi:10.1038/s41598-020-78293-3

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MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells

MPS-Authors

Kapoor, Tanya
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Corrado, Mauro
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce, Erika L.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce, Edward J.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Grosschedl, Rudolf
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.nature.com/articles/s41598-020-78293-3
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Citation

Kapoor, T., Corrado, M., Pearce, E. L., Pearce, E. J., & Grosschedl, R. (2020). MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells. Scientific Reports, 10: 21626. doi:10.1038/s41598-020-78293-3.

Cite as: https://hdl.handle.net/21.11116/0000-0007-E718-A

Abstract

MZB1 is an endoplasmic reticulum (ER)-resident protein that plays an important role in the humoral immune response by enhancing the interaction of the μ immunoglobulin (Ig) heavy chain with the chaperone GRP94 and by augmenting the secretion of IgM. Here, we show that MZB1 is also expressed in plasmacytoid dendritic cells (pDCs). Mzb1^−/− pDCs have a defect in the secretion of interferon (IFN) α upon Toll-like receptor (TLR) 9 stimulation and a reduced ability to enhance B cell differentiation towards plasma cells. Mzb1^−/− pDCs do not properly expand the ER upon TLR9 stimulation, which may be accounted for by an impaired activation of ATF6, a regulator of the unfolded protein response (UPR). Pharmacological inhibition of ATF6 cleavage in stimulated wild type pDCs mimics the diminished IFNα secretion by Mzb1^−/− pDCs. Thus, MZB1 enables pDCs to secrete high amounts of IFNα by mitigating ER stress via the ATF6-mediated UPR.