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  MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells

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.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0007-E718-A Version Permalink: https://hdl.handle.net/21.11116/0000-0009-F680-0
Genre: Journal Article

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Kapoor et al. 2020.pdf (Publisher version), 3MB
 
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2020
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https://www.nature.com/articles/s41598-020-78293-3 (Publisher version)
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 Creators:
Kapoor, Tanya1, Author
Corrado, Mauro2, Author           
Pearce, Erika L.2, Author           
Pearce, Edward J.2, Author           
Grosschedl, Rudolf1, Author           
Affiliations:
1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
2Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              

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 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.

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Language(s): eng - English
 Dates: 2020-12-14
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41598-020-78293-3
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Title: Scientific Reports
  Abbreviation : Sci. Rep.
Source Genre: Journal
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Publ. Info: London, UK : Nature Publishing Group
Pages: - Volume / Issue: 10 Sequence Number: 21626 Start / End Page: - Identifier: ISSN: 2045-2322
CoNE: https://pure.mpg.de/cone/journals/resource/2045-2322