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The Lack of STING Impairs the MHC-I Dependent Antigen Presentation and JAK/STAT Signaling in Murine Macrophages

STING is a transmembrane ER resident protein that was initially described as a regulator of innate immune response triggered by viral DNA and later found to be involved in a broader range of immune processes. Here, we assessed its role in the antigen presentation by generating a STING KO macrophage...

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Autores principales: Caiazza, Carmen, Brusco, Teresa, D’Alessio, Federica, D’Agostino, Massimo, Avagliano, Angelica, Arcucci, Alessandro, Ambrosino, Concetta, Fiume, Giuseppe, Mallardo, Massimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697192/
https://www.ncbi.nlm.nih.gov/pubmed/36430709
http://dx.doi.org/10.3390/ijms232214232
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author Caiazza, Carmen
Brusco, Teresa
D’Alessio, Federica
D’Agostino, Massimo
Avagliano, Angelica
Arcucci, Alessandro
Ambrosino, Concetta
Fiume, Giuseppe
Mallardo, Massimo
author_facet Caiazza, Carmen
Brusco, Teresa
D’Alessio, Federica
D’Agostino, Massimo
Avagliano, Angelica
Arcucci, Alessandro
Ambrosino, Concetta
Fiume, Giuseppe
Mallardo, Massimo
author_sort Caiazza, Carmen
collection PubMed
description STING is a transmembrane ER resident protein that was initially described as a regulator of innate immune response triggered by viral DNA and later found to be involved in a broader range of immune processes. Here, we assessed its role in the antigen presentation by generating a STING KO macrophage cell line. In the absence of STING, we observed an impaired OVA-derived SIINFEKL peptide presentation together with a decreased level of MHC-I complex on the plasma membrane, likely due to a decreased mRNA expression of β2 m light chain as no relevant alterations of the peptide-loading complex (TAPs) were found. Moreover, JAK-STAT signaling resulted in impaired STING KO cells following OVA and LPS treatments, suggesting a dampened activation of immune response. Our data revealed a new molecular role of STING in immune mechanisms that could elucidate its role in the pathogenesis of autoimmune disorders and cancer.
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spelling pubmed-96971922022-11-26 The Lack of STING Impairs the MHC-I Dependent Antigen Presentation and JAK/STAT Signaling in Murine Macrophages Caiazza, Carmen Brusco, Teresa D’Alessio, Federica D’Agostino, Massimo Avagliano, Angelica Arcucci, Alessandro Ambrosino, Concetta Fiume, Giuseppe Mallardo, Massimo Int J Mol Sci Article STING is a transmembrane ER resident protein that was initially described as a regulator of innate immune response triggered by viral DNA and later found to be involved in a broader range of immune processes. Here, we assessed its role in the antigen presentation by generating a STING KO macrophage cell line. In the absence of STING, we observed an impaired OVA-derived SIINFEKL peptide presentation together with a decreased level of MHC-I complex on the plasma membrane, likely due to a decreased mRNA expression of β2 m light chain as no relevant alterations of the peptide-loading complex (TAPs) were found. Moreover, JAK-STAT signaling resulted in impaired STING KO cells following OVA and LPS treatments, suggesting a dampened activation of immune response. Our data revealed a new molecular role of STING in immune mechanisms that could elucidate its role in the pathogenesis of autoimmune disorders and cancer. MDPI 2022-11-17 /pmc/articles/PMC9697192/ /pubmed/36430709 http://dx.doi.org/10.3390/ijms232214232 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Caiazza, Carmen
Brusco, Teresa
D’Alessio, Federica
D’Agostino, Massimo
Avagliano, Angelica
Arcucci, Alessandro
Ambrosino, Concetta
Fiume, Giuseppe
Mallardo, Massimo
The Lack of STING Impairs the MHC-I Dependent Antigen Presentation and JAK/STAT Signaling in Murine Macrophages
title The Lack of STING Impairs the MHC-I Dependent Antigen Presentation and JAK/STAT Signaling in Murine Macrophages
title_full The Lack of STING Impairs the MHC-I Dependent Antigen Presentation and JAK/STAT Signaling in Murine Macrophages
title_fullStr The Lack of STING Impairs the MHC-I Dependent Antigen Presentation and JAK/STAT Signaling in Murine Macrophages
title_full_unstemmed The Lack of STING Impairs the MHC-I Dependent Antigen Presentation and JAK/STAT Signaling in Murine Macrophages
title_short The Lack of STING Impairs the MHC-I Dependent Antigen Presentation and JAK/STAT Signaling in Murine Macrophages
title_sort lack of sting impairs the mhc-i dependent antigen presentation and jak/stat signaling in murine macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697192/
https://www.ncbi.nlm.nih.gov/pubmed/36430709
http://dx.doi.org/10.3390/ijms232214232
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