Inhibition of PI3Kδ Differentially Regulates Poly I:C– and Human Metapneumovirus–Induced PD–L1 and PD–L2 Expression in Human Bronchial Epithelial Cells

Bronchial epithelial cells are front sentinels eliciting innate and adaptive immunity to respiratory viral pathogens. Recognition of viral double-stranded RNA induces antiviral interferon (IFN) responses in bronchial epithelial cells. Co-inhibitory molecules programmed cell death 1 ligand 1 (PD-L1)...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tomohiro Ogawa, Keiko Kan-o, Ayaka Shiota, Akitaka Fujita, Yumiko Ishii, Satoru Fukuyama, Koichiro Matsumoto
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	programmed cell death 1 ligand 1 programmed cell death 1 ligand 2 interferon phosphoinositide 3-kinase delta bronchial epithelial cells human metapneumovirus Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/328b4c37b8d443b3acbf832981a32c29
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:328b4c37b8d443b3acbf832981a32c29
record_format	dspace
spelling	oai:doaj.org-article:328b4c37b8d443b3acbf832981a32c292021-12-01T02:16:09ZInhibition of PI3Kδ Differentially Regulates Poly I:C– and Human Metapneumovirus–Induced PD–L1 and PD–L2 Expression in Human Bronchial Epithelial Cells1664-322410.3389/fimmu.2021.767666https://doaj.org/article/328b4c37b8d443b3acbf832981a32c292021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.767666/fullhttps://doaj.org/toc/1664-3224Bronchial epithelial cells are front sentinels eliciting innate and adaptive immunity to respiratory viral pathogens. Recognition of viral double-stranded RNA induces antiviral interferon (IFN) responses in bronchial epithelial cells. Co-inhibitory molecules programmed cell death 1 ligand 1 (PD-L1) and ligand 2 (PD-L2) were also induced on bronchial epithelial cells, which bind programmed cell death 1 on T cell and inhibit the function of virus-specific cytotoxic T lymphocyte. A previous study showed that antiviral type I IFN increased PD-L1 and PD-L2 expression in cultured melanoma cells. However, it remains unknown whether antiviral IFNs affect PD-L1 and PD-L2 expression in bronchial epithelial cells. In addition, we previously reported that inhibition of PI3Kδ signaling enhanced antiviral IFN responses in human primary bronchial epithelial cells (PBECs). Here we assessed the effect of exogenous IFNs or a selective PI3Kδ inhibitor IC87114 on PD-L1 and PD-L2 in PBECs stimulated with a synthetic double-stranded RNA poly I:C or human metapneumovirus. Treatment with IFNβ or IFNλ increased PD-L1 and PD-L2, and IFNβ or IFNλ treatment plus poly I:C further increased both expressions. Treatment with IC87114 or transfection with siRNA targeting PI3K p110δ enhanced poly I:C–induced gene and protein expression of PD-L2, whereas IC87114 suppressed poly I:C–induced PD-L1. IC87114 enhanced poly I:C–induced gene expression of IFNβ, IFNλ, and IFN-regulated genes via increased TBK1 and IRF3 phosphorylation. Transfection with siIRF3 counteracted the enhancement of poly I:C–induced PD-L2 by IC87114, whereas IC87114 suppressed poly I:C–induced PD-L1 regardless of transfection with siNC or siIRF3. Similar effects of IC87114 on PD-L1 and PD-L2 expression were observed in human metapneumovirus–infected PBECs. We showed for the first time that type I and type III IFNs induced the expression of PD-L1 and PD-L2 in PBECs. Our findings suggest that during viral infections, inhibition of PI3Kδ differentially regulates PD-L1 and PD-L2 expression in bronchial epithelial cells.Tomohiro OgawaKeiko Kan-oKeiko Kan-oAyaka ShiotaAkitaka FujitaYumiko IshiiSatoru FukuyamaKoichiro MatsumotoFrontiers Media S.A.articleprogrammed cell death 1 ligand 1programmed cell death 1 ligand 2interferonphosphoinositide 3-kinase deltabronchial epithelial cellshuman metapneumovirusImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	programmed cell death 1 ligand 1 programmed cell death 1 ligand 2 interferon phosphoinositide 3-kinase delta bronchial epithelial cells human metapneumovirus Immunologic diseases. Allergy RC581-607
spellingShingle	programmed cell death 1 ligand 1 programmed cell death 1 ligand 2 interferon phosphoinositide 3-kinase delta bronchial epithelial cells human metapneumovirus Immunologic diseases. Allergy RC581-607 Tomohiro Ogawa Keiko Kan-o Keiko Kan-o Ayaka Shiota Akitaka Fujita Yumiko Ishii Satoru Fukuyama Koichiro Matsumoto Inhibition of PI3Kδ Differentially Regulates Poly I:C– and Human Metapneumovirus–Induced PD–L1 and PD–L2 Expression in Human Bronchial Epithelial Cells
description	Bronchial epithelial cells are front sentinels eliciting innate and adaptive immunity to respiratory viral pathogens. Recognition of viral double-stranded RNA induces antiviral interferon (IFN) responses in bronchial epithelial cells. Co-inhibitory molecules programmed cell death 1 ligand 1 (PD-L1) and ligand 2 (PD-L2) were also induced on bronchial epithelial cells, which bind programmed cell death 1 on T cell and inhibit the function of virus-specific cytotoxic T lymphocyte. A previous study showed that antiviral type I IFN increased PD-L1 and PD-L2 expression in cultured melanoma cells. However, it remains unknown whether antiviral IFNs affect PD-L1 and PD-L2 expression in bronchial epithelial cells. In addition, we previously reported that inhibition of PI3Kδ signaling enhanced antiviral IFN responses in human primary bronchial epithelial cells (PBECs). Here we assessed the effect of exogenous IFNs or a selective PI3Kδ inhibitor IC87114 on PD-L1 and PD-L2 in PBECs stimulated with a synthetic double-stranded RNA poly I:C or human metapneumovirus. Treatment with IFNβ or IFNλ increased PD-L1 and PD-L2, and IFNβ or IFNλ treatment plus poly I:C further increased both expressions. Treatment with IC87114 or transfection with siRNA targeting PI3K p110δ enhanced poly I:C–induced gene and protein expression of PD-L2, whereas IC87114 suppressed poly I:C–induced PD-L1. IC87114 enhanced poly I:C–induced gene expression of IFNβ, IFNλ, and IFN-regulated genes via increased TBK1 and IRF3 phosphorylation. Transfection with siIRF3 counteracted the enhancement of poly I:C–induced PD-L2 by IC87114, whereas IC87114 suppressed poly I:C–induced PD-L1 regardless of transfection with siNC or siIRF3. Similar effects of IC87114 on PD-L1 and PD-L2 expression were observed in human metapneumovirus–infected PBECs. We showed for the first time that type I and type III IFNs induced the expression of PD-L1 and PD-L2 in PBECs. Our findings suggest that during viral infections, inhibition of PI3Kδ differentially regulates PD-L1 and PD-L2 expression in bronchial epithelial cells.
format	article
author	Tomohiro Ogawa Keiko Kan-o Keiko Kan-o Ayaka Shiota Akitaka Fujita Yumiko Ishii Satoru Fukuyama Koichiro Matsumoto
author_facet	Tomohiro Ogawa Keiko Kan-o Keiko Kan-o Ayaka Shiota Akitaka Fujita Yumiko Ishii Satoru Fukuyama Koichiro Matsumoto
author_sort	Tomohiro Ogawa
title	Inhibition of PI3Kδ Differentially Regulates Poly I:C– and Human Metapneumovirus–Induced PD–L1 and PD–L2 Expression in Human Bronchial Epithelial Cells
title_short	Inhibition of PI3Kδ Differentially Regulates Poly I:C– and Human Metapneumovirus–Induced PD–L1 and PD–L2 Expression in Human Bronchial Epithelial Cells
title_full	Inhibition of PI3Kδ Differentially Regulates Poly I:C– and Human Metapneumovirus–Induced PD–L1 and PD–L2 Expression in Human Bronchial Epithelial Cells
title_fullStr	Inhibition of PI3Kδ Differentially Regulates Poly I:C– and Human Metapneumovirus–Induced PD–L1 and PD–L2 Expression in Human Bronchial Epithelial Cells
title_full_unstemmed	Inhibition of PI3Kδ Differentially Regulates Poly I:C– and Human Metapneumovirus–Induced PD–L1 and PD–L2 Expression in Human Bronchial Epithelial Cells
title_sort	inhibition of pi3kδ differentially regulates poly i:c– and human metapneumovirus–induced pd–l1 and pd–l2 expression in human bronchial epithelial cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/328b4c37b8d443b3acbf832981a32c29
work_keys_str_mv	AT tomohiroogawa inhibitionofpi3kddifferentiallyregulatespolyicandhumanmetapneumovirusinducedpdl1andpdl2expressioninhumanbronchialepithelialcells AT keikokano inhibitionofpi3kddifferentiallyregulatespolyicandhumanmetapneumovirusinducedpdl1andpdl2expressioninhumanbronchialepithelialcells AT keikokano inhibitionofpi3kddifferentiallyregulatespolyicandhumanmetapneumovirusinducedpdl1andpdl2expressioninhumanbronchialepithelialcells AT ayakashiota inhibitionofpi3kddifferentiallyregulatespolyicandhumanmetapneumovirusinducedpdl1andpdl2expressioninhumanbronchialepithelialcells AT akitakafujita inhibitionofpi3kddifferentiallyregulatespolyicandhumanmetapneumovirusinducedpdl1andpdl2expressioninhumanbronchialepithelialcells AT yumikoishii inhibitionofpi3kddifferentiallyregulatespolyicandhumanmetapneumovirusinducedpdl1andpdl2expressioninhumanbronchialepithelialcells AT satorufukuyama inhibitionofpi3kddifferentiallyregulatespolyicandhumanmetapneumovirusinducedpdl1andpdl2expressioninhumanbronchialepithelialcells AT koichiromatsumoto inhibitionofpi3kddifferentiallyregulatespolyicandhumanmetapneumovirusinducedpdl1andpdl2expressioninhumanbronchialepithelialcells
_version_	1718405895102136320

Inhibition of PI3Kδ Differentially Regulates Poly I:C– and Human Metapneumovirus–Induced PD–L1 and PD–L2 Expression in Human Bronchial Epithelial Cells

Ejemplares similares