Tunable heat shock protein-mediated NK cell responses are orchestrated by STAT1 in Antigen Presenting Cells

Abstract The release of Heat Shock Proteins (HSPs) from aberrant cells can initiate immune responses following engagement of the HSPs with antigen presenting cells (APCs). This is an important mechanism for cancer immunosurveillance and can also be modeled by vaccination with HSPs through various ro...

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Autores principales:	Abigail L. Sedlacek, Lauren B. Kinner-Bibeau, Yifei Wang, Alicia P. Mizes, Robert J. Binder
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/97d4f75192d24757a9d884d4ad3eb92d
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spelling	oai:doaj.org-article:97d4f75192d24757a9d884d4ad3eb92d2021-12-02T19:06:44ZTunable heat shock protein-mediated NK cell responses are orchestrated by STAT1 in Antigen Presenting Cells10.1038/s41598-021-95578-32045-2322https://doaj.org/article/97d4f75192d24757a9d884d4ad3eb92d2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95578-3https://doaj.org/toc/2045-2322Abstract The release of Heat Shock Proteins (HSPs) from aberrant cells can initiate immune responses following engagement of the HSPs with antigen presenting cells (APCs). This is an important mechanism for cancer immunosurveillance and can also be modeled by vaccination with HSPs through various routes, targeting specific APCs expressing the HSP receptor CD91. Immunological outcomes can be varied as a result of the broad expression of CD91 in different dendritic cell and macrophage populations. We investigated the cellular response of different APCs to the prototypical immunogenic HSP, gp96, in the context of Th1 immunity. Although APCs generally express similar levels of the HSP receptor CD91, we uncovered APC-distinct, downstream signaling pathways activating STAT1, and differential STAT1 induced genes. As a result of this differential and unique signaling we determined that gp96-activated macrophages, but not DCs are capable of activating NK cells to produce IFN- $$\gamma$$ γ . These data demonstrate that different APC subsets elicit unique intracellular signaling responses to HSPs which result in different patterns of downstream cellular activation and immune responses. Collectively this provides a novel tunable and autochthonous immune response to extracellular HSPs which has important implications on the development of immunity to cancer and infectious disease, as well as homeostasis.Abigail L. SedlacekLauren B. Kinner-BibeauYifei WangAlicia P. MizesRobert J. BinderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abigail L. Sedlacek Lauren B. Kinner-Bibeau Yifei Wang Alicia P. Mizes Robert J. Binder Tunable heat shock protein-mediated NK cell responses are orchestrated by STAT1 in Antigen Presenting Cells
description	Abstract The release of Heat Shock Proteins (HSPs) from aberrant cells can initiate immune responses following engagement of the HSPs with antigen presenting cells (APCs). This is an important mechanism for cancer immunosurveillance and can also be modeled by vaccination with HSPs through various routes, targeting specific APCs expressing the HSP receptor CD91. Immunological outcomes can be varied as a result of the broad expression of CD91 in different dendritic cell and macrophage populations. We investigated the cellular response of different APCs to the prototypical immunogenic HSP, gp96, in the context of Th1 immunity. Although APCs generally express similar levels of the HSP receptor CD91, we uncovered APC-distinct, downstream signaling pathways activating STAT1, and differential STAT1 induced genes. As a result of this differential and unique signaling we determined that gp96-activated macrophages, but not DCs are capable of activating NK cells to produce IFN- $$\gamma$$ γ . These data demonstrate that different APC subsets elicit unique intracellular signaling responses to HSPs which result in different patterns of downstream cellular activation and immune responses. Collectively this provides a novel tunable and autochthonous immune response to extracellular HSPs which has important implications on the development of immunity to cancer and infectious disease, as well as homeostasis.
format	article
author	Abigail L. Sedlacek Lauren B. Kinner-Bibeau Yifei Wang Alicia P. Mizes Robert J. Binder
author_facet	Abigail L. Sedlacek Lauren B. Kinner-Bibeau Yifei Wang Alicia P. Mizes Robert J. Binder
author_sort	Abigail L. Sedlacek
title	Tunable heat shock protein-mediated NK cell responses are orchestrated by STAT1 in Antigen Presenting Cells
title_short	Tunable heat shock protein-mediated NK cell responses are orchestrated by STAT1 in Antigen Presenting Cells
title_full	Tunable heat shock protein-mediated NK cell responses are orchestrated by STAT1 in Antigen Presenting Cells
title_fullStr	Tunable heat shock protein-mediated NK cell responses are orchestrated by STAT1 in Antigen Presenting Cells
title_full_unstemmed	Tunable heat shock protein-mediated NK cell responses are orchestrated by STAT1 in Antigen Presenting Cells
title_sort	tunable heat shock protein-mediated nk cell responses are orchestrated by stat1 in antigen presenting cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/97d4f75192d24757a9d884d4ad3eb92d
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Tunable heat shock protein-mediated NK cell responses are orchestrated by STAT1 in Antigen Presenting Cells

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