MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number21626
JournalScientific reports
Issue number1
StatePublished - Dec 2020
Externally publishedYes

ASJC Scopus subject areas

  • General


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