MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells

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...

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Autores principales:	Tanya Kapoor, Mauro Corrado, Erika L. Pearce, Edward J. Pearce, Rudolf Grosschedl
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/972697e64b8a4a0083614fad217f537c
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spelling	oai:doaj.org-article:972697e64b8a4a0083614fad217f537c2021-12-02T13:58:15ZMZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells10.1038/s41598-020-78293-32045-2322https://doaj.org/article/972697e64b8a4a0083614fad217f537c2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78293-3https://doaj.org/toc/2045-2322Abstract 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.Tanya KapoorMauro CorradoErika L. PearceEdward J. PearceRudolf GrosschedlNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tanya Kapoor Mauro Corrado Erika L. Pearce Edward J. Pearce Rudolf Grosschedl MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells
description	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.
format	article
author	Tanya Kapoor Mauro Corrado Erika L. Pearce Edward J. Pearce Rudolf Grosschedl
author_facet	Tanya Kapoor Mauro Corrado Erika L. Pearce Edward J. Pearce Rudolf Grosschedl
author_sort	Tanya Kapoor
title	MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells
title_short	MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells
title_full	MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells
title_fullStr	MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells
title_full_unstemmed	MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells
title_sort	mzb1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/972697e64b8a4a0083614fad217f537c
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MZB1 enables efficient interferon α secretion in stimulated plasmacytoid dendritic cells

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