Human Decidual CD1a<sup>+</sup> Dendritic Cells Undergo Functional Maturation Program Mediated by Gp96

Heat shock proteins (hsps), in certain circumstances, could shape unique features of decidual dendritic cells (DCs) that play a key role in inducing immunity as well as maintaining tolerance. The aim of the study was to assess the binding of gp96 to Toll-like receptor (TLR) 4 and CD91 receptors on d...

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Main Authors: Tamara Gulic, Gordana Laskarin, Lana Glavan, Tanja Grubić Kezele, Herman Haller, Daniel Rukavina
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/3/2278
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author Tamara Gulic
Gordana Laskarin
Lana Glavan
Tanja Grubić Kezele
Herman Haller
Daniel Rukavina
author_facet Tamara Gulic
Gordana Laskarin
Lana Glavan
Tanja Grubić Kezele
Herman Haller
Daniel Rukavina
author_sort Tamara Gulic
collection DOAJ
description Heat shock proteins (hsps), in certain circumstances, could shape unique features of decidual dendritic cells (DCs) that play a key role in inducing immunity as well as maintaining tolerance. The aim of the study was to assess the binding of gp96 to Toll-like receptor (TLR) 4 and CD91 receptors on decidual CD1a<sup>+</sup> DCs present at the maternal-fetal interface in vitro as well as the influence of CD1a<sup>+</sup> DCs maturation status. Immunohistology and immunofluorescence of paraffin-embedded first-trimester decidua tissue sections of normal and pathological (missed abortion MA and blighted ovum BO) pregnancies were performed together with flow cytometry detection of antigens in CD1a<sup>+</sup> DCs after gp96 stimulation of decidual mononuclear cells. Gp96 efficiently bound CD91 and TLR4 receptors on decidual CD1a<sup>+</sup> DCs in a dose-dependent manner and increased the expression of CD83 and HLA-DR. The highest concentration of gp96 (1000 ng/mL) increased the percentage of Interferon-γ (INF-γ) and IL-15 expressing gp96<sup>+</sup> cells. Gp96 binds CD91 and TLR4 on decidual CD1a<sup>+</sup> DCs, which causes their maturation and significantly increases INF-γ and IL-15 in the context of Th1 cytokine/chemokine domination, which could support immune response harmful for ongoing pregnancy.
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spelling doaj.art-e0c3fd4ad3c342d3988eac05746927b42023-11-16T16:54:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243227810.3390/ijms24032278Human Decidual CD1a<sup>+</sup> Dendritic Cells Undergo Functional Maturation Program Mediated by Gp96Tamara Gulic0Gordana Laskarin1Lana Glavan2Tanja Grubić Kezele3Herman Haller4Daniel Rukavina5Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, CroatiaDepartment of Physiology and Immunology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, CroatiaDepartment of Obstetrics and Gynecology, Clinical Hospital Rijeka, University of Rijeka, Kresimirova 42a, 51000 Rijeka, CroatiaDepartment of Physiology and Immunology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, CroatiaDepartment of Obstetrics and Gynecology, Clinical Hospital Rijeka, University of Rijeka, Kresimirova 42a, 51000 Rijeka, CroatiaDepartment of Physiology and Immunology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, CroatiaHeat shock proteins (hsps), in certain circumstances, could shape unique features of decidual dendritic cells (DCs) that play a key role in inducing immunity as well as maintaining tolerance. The aim of the study was to assess the binding of gp96 to Toll-like receptor (TLR) 4 and CD91 receptors on decidual CD1a<sup>+</sup> DCs present at the maternal-fetal interface in vitro as well as the influence of CD1a<sup>+</sup> DCs maturation status. Immunohistology and immunofluorescence of paraffin-embedded first-trimester decidua tissue sections of normal and pathological (missed abortion MA and blighted ovum BO) pregnancies were performed together with flow cytometry detection of antigens in CD1a<sup>+</sup> DCs after gp96 stimulation of decidual mononuclear cells. Gp96 efficiently bound CD91 and TLR4 receptors on decidual CD1a<sup>+</sup> DCs in a dose-dependent manner and increased the expression of CD83 and HLA-DR. The highest concentration of gp96 (1000 ng/mL) increased the percentage of Interferon-γ (INF-γ) and IL-15 expressing gp96<sup>+</sup> cells. Gp96 binds CD91 and TLR4 on decidual CD1a<sup>+</sup> DCs, which causes their maturation and significantly increases INF-γ and IL-15 in the context of Th1 cytokine/chemokine domination, which could support immune response harmful for ongoing pregnancy.https://www.mdpi.com/1422-0067/24/3/2278decidual dendritic cellschemokinecytokinegp96pregnancy
spellingShingle Tamara Gulic
Gordana Laskarin
Lana Glavan
Tanja Grubić Kezele
Herman Haller
Daniel Rukavina
Human Decidual CD1a<sup>+</sup> Dendritic Cells Undergo Functional Maturation Program Mediated by Gp96
International Journal of Molecular Sciences
decidual dendritic cells
chemokine
cytokine
gp96
pregnancy
title Human Decidual CD1a<sup>+</sup> Dendritic Cells Undergo Functional Maturation Program Mediated by Gp96
title_full Human Decidual CD1a<sup>+</sup> Dendritic Cells Undergo Functional Maturation Program Mediated by Gp96
title_fullStr Human Decidual CD1a<sup>+</sup> Dendritic Cells Undergo Functional Maturation Program Mediated by Gp96
title_full_unstemmed Human Decidual CD1a<sup>+</sup> Dendritic Cells Undergo Functional Maturation Program Mediated by Gp96
title_short Human Decidual CD1a<sup>+</sup> Dendritic Cells Undergo Functional Maturation Program Mediated by Gp96
title_sort human decidual cd1a sup sup dendritic cells undergo functional maturation program mediated by gp96
topic decidual dendritic cells
chemokine
cytokine
gp96
pregnancy
url https://www.mdpi.com/1422-0067/24/3/2278
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AT lanaglavan humandecidualcd1asupsupdendriticcellsundergofunctionalmaturationprogrammediatedbygp96
AT tanjagrubickezele humandecidualcd1asupsupdendriticcellsundergofunctionalmaturationprogrammediatedbygp96
AT hermanhaller humandecidualcd1asupsupdendriticcellsundergofunctionalmaturationprogrammediatedbygp96
AT danielrukavina humandecidualcd1asupsupdendriticcellsundergofunctionalmaturationprogrammediatedbygp96