| First Author | Kapoor T | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 21626 |
| PubMed ID | 33318509 | Mgi Jnum | J:321020 |
| Mgi Id | MGI:6741258 | Doi | 10.1038/s41598-020-78293-3 |
| Citation | Kapoor T, et al. (2020) MZB1 enables efficient interferon alpha secretion in stimulated plasmacytoid dendritic cells. Sci Rep 10(1):21626 |
| abstractText | MZB1 is an endoplasmic reticulum (ER)-resident protein that plays an important role in the humoral immune response by enhancing the interaction of the mu 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) alpha 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 IFNalpha secretion by Mzb1(-/-) pDCs. Thus, MZB1 enables pDCs to secrete high amounts of IFNalpha by mitigating ER stress via the ATF6-mediated UPR. |
