Secretomes derived from osteogenically differentiated jaw periosteal cells inhibit phenotypic and functional maturation of CD14+ monocyte-derived dendritic cells

The jaw periosteal tissue is generally recognized as a suitable source for the isolation of mesenchymal stem cells (MSCs). In previous studies we showed evidence that two- and three-dimensionally cultured jaw periosteum-derived MSCs (JPCs) are able to induce a more immature phenotype of dendritic ce...

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Main Authors: Wanjing Cen, Felix Umrath, António José Salgado, Siegmar Reinert, Dorothea Alexander
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.1024509/full
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author Wanjing Cen
Felix Umrath
Felix Umrath
António José Salgado
António José Salgado
Siegmar Reinert
Dorothea Alexander
author_facet Wanjing Cen
Felix Umrath
Felix Umrath
António José Salgado
António José Salgado
Siegmar Reinert
Dorothea Alexander
author_sort Wanjing Cen
collection DOAJ
description The jaw periosteal tissue is generally recognized as a suitable source for the isolation of mesenchymal stem cells (MSCs). In previous studies we showed evidence that two- and three-dimensionally cultured jaw periosteum-derived MSCs (JPCs) are able to induce a more immature phenotype of dendritic cells (DCs). To further expand our knowledge of JPCs’ immunoregulative function, we investigated the effects of JPC secretomes derived from undifferentiated (CO) or osteogenically differentiated cells (treated with or without dexamethasone: OB+/-D) on CD14+ monocyte-derived DCs (MoDCs). We detected a remarkably reduced formation of MoDC homotypic clusters under the influence of secretomes from osteogenically induced JPCs. Further, significantly decreased numbers of CD83+ cells, up-regulated CD209 and down-regulated CD80, CD86 and CD197 expression levels were detected on the surface of MoDCs. Whereas secretomes from JPCs osteogenically stimulated with dexamethasone significantly enhanced FITC-dextran uptake capacity of MoDCs, the increase by secretomes of JPCs treated without dexamethasone did not reach significance. The analysis of mixed lymphocyte reactions revealed that OB+/-D secretomes were able to significantly reduce the numbers of proliferating CD14- peripheral blood mononuclear cells (PBMCs) and of proliferating CD4+ T cells. The OB-D secretome significantly promoted the expansion of regulatory CD25+ T cells. Regarding gene expression of MoDCs, remarkably up-regulated mRNA expression of CD209, HLA-DRA, CSF3, IL10 and IL8 was detected when DCs were cultured in the presence of OB+/-D secretomes. At the same time, secretomes seemed to have an impact in the down-regulation of IFNγ and IL12B gene expression. At protein level, OB+/-D secretomes significantly up-regulated IL-10 and IDO (indoleamine-pyrrole 2,3-dioxygenase) levels whereas IL-12/IL-23p40 levels were down-regulated in supernatants of MoDCs when cultured under the presence of OB+/-D secretomes. Taken together, while secretomes from untreated JPCs had only little effects on the process of maturation of MoDCs, secretomes derived from osteogenically induced JPCs were able to inhibit the phenotypic and functional maturation of MoDCs.
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spelling doaj.art-d1fd1b189d6a4fd39964a798cdfb6c9b2023-01-09T11:19:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.10245091024509Secretomes derived from osteogenically differentiated jaw periosteal cells inhibit phenotypic and functional maturation of CD14+ monocyte-derived dendritic cellsWanjing Cen0Felix Umrath1Felix Umrath2António José Salgado3António José Salgado4Siegmar Reinert5Dorothea Alexander6Department of Oral and Maxillofacial Surgery, University Hospital Tübingen, Tübingen, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Tübingen, Tübingen, GermanyClinic for Orthopaedic Surgery, University Hospital Tübingen, Tübingen, GermanyLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, PortugalICVS/3B’s-PT Government Associate Laboratory, University of Minho, Braga, PortugalDepartment of Oral and Maxillofacial Surgery, University Hospital Tübingen, Tübingen, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Tübingen, Tübingen, GermanyThe jaw periosteal tissue is generally recognized as a suitable source for the isolation of mesenchymal stem cells (MSCs). In previous studies we showed evidence that two- and three-dimensionally cultured jaw periosteum-derived MSCs (JPCs) are able to induce a more immature phenotype of dendritic cells (DCs). To further expand our knowledge of JPCs’ immunoregulative function, we investigated the effects of JPC secretomes derived from undifferentiated (CO) or osteogenically differentiated cells (treated with or without dexamethasone: OB+/-D) on CD14+ monocyte-derived DCs (MoDCs). We detected a remarkably reduced formation of MoDC homotypic clusters under the influence of secretomes from osteogenically induced JPCs. Further, significantly decreased numbers of CD83+ cells, up-regulated CD209 and down-regulated CD80, CD86 and CD197 expression levels were detected on the surface of MoDCs. Whereas secretomes from JPCs osteogenically stimulated with dexamethasone significantly enhanced FITC-dextran uptake capacity of MoDCs, the increase by secretomes of JPCs treated without dexamethasone did not reach significance. The analysis of mixed lymphocyte reactions revealed that OB+/-D secretomes were able to significantly reduce the numbers of proliferating CD14- peripheral blood mononuclear cells (PBMCs) and of proliferating CD4+ T cells. The OB-D secretome significantly promoted the expansion of regulatory CD25+ T cells. Regarding gene expression of MoDCs, remarkably up-regulated mRNA expression of CD209, HLA-DRA, CSF3, IL10 and IL8 was detected when DCs were cultured in the presence of OB+/-D secretomes. At the same time, secretomes seemed to have an impact in the down-regulation of IFNγ and IL12B gene expression. At protein level, OB+/-D secretomes significantly up-regulated IL-10 and IDO (indoleamine-pyrrole 2,3-dioxygenase) levels whereas IL-12/IL-23p40 levels were down-regulated in supernatants of MoDCs when cultured under the presence of OB+/-D secretomes. Taken together, while secretomes from untreated JPCs had only little effects on the process of maturation of MoDCs, secretomes derived from osteogenically induced JPCs were able to inhibit the phenotypic and functional maturation of MoDCs.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1024509/fullmesenchymal stem cellsjaw periosteal cellsosteogenic differentiationsecretomesCD14+ monocytesdendritic cell maturation
spellingShingle Wanjing Cen
Felix Umrath
Felix Umrath
António José Salgado
António José Salgado
Siegmar Reinert
Dorothea Alexander
Secretomes derived from osteogenically differentiated jaw periosteal cells inhibit phenotypic and functional maturation of CD14+ monocyte-derived dendritic cells
Frontiers in Immunology
mesenchymal stem cells
jaw periosteal cells
osteogenic differentiation
secretomes
CD14+ monocytes
dendritic cell maturation
title Secretomes derived from osteogenically differentiated jaw periosteal cells inhibit phenotypic and functional maturation of CD14+ monocyte-derived dendritic cells
title_full Secretomes derived from osteogenically differentiated jaw periosteal cells inhibit phenotypic and functional maturation of CD14+ monocyte-derived dendritic cells
title_fullStr Secretomes derived from osteogenically differentiated jaw periosteal cells inhibit phenotypic and functional maturation of CD14+ monocyte-derived dendritic cells
title_full_unstemmed Secretomes derived from osteogenically differentiated jaw periosteal cells inhibit phenotypic and functional maturation of CD14+ monocyte-derived dendritic cells
title_short Secretomes derived from osteogenically differentiated jaw periosteal cells inhibit phenotypic and functional maturation of CD14+ monocyte-derived dendritic cells
title_sort secretomes derived from osteogenically differentiated jaw periosteal cells inhibit phenotypic and functional maturation of cd14 monocyte derived dendritic cells
topic mesenchymal stem cells
jaw periosteal cells
osteogenic differentiation
secretomes
CD14+ monocytes
dendritic cell maturation
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.1024509/full
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