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Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c-Fos and ATP6V0D2

Osteoimmunological studies have revealed that T cells exert a powerful impact on the formation and activity of osteoclasts and bone remodeling. Evidence demonstrates that immature dendritic cells (iDCs) are more efficient transdifferentiating into osteoclasts (OCs) than monocytes. However, whether V...

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Autores principales: Zhu, Xiaolin, Zeng, Zhiyong, Qiu, Dongbiao, Chen, Junmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108864/
https://www.ncbi.nlm.nih.gov/pubmed/30066839
http://dx.doi.org/10.3892/ijmm.2018.3791
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author Zhu, Xiaolin
Zeng, Zhiyong
Qiu, Dongbiao
Chen, Junmin
author_facet Zhu, Xiaolin
Zeng, Zhiyong
Qiu, Dongbiao
Chen, Junmin
author_sort Zhu, Xiaolin
collection PubMed
description Osteoimmunological studies have revealed that T cells exert a powerful impact on the formation and activity of osteoclasts and bone remodeling. Evidence demonstrates that immature dendritic cells (iDCs) are more efficient transdifferentiating into osteoclasts (OCs) than monocytes. However, whether Vγ9Vδ2 T (γδ T) cells stimulate or inhibit iDC transdifferentiation into OCs has never been reported. The aim of the present study was to investigate the effects of γδ T cells on this transdifferentiation process. γδ T cells and iDCs were isolated from the peripheral blood of healthy volunteers separately and were co-cultured with Transwelll inserts, with γδ T cells in the upper chamber and iDCs in the lower chamber. IDCs were treated with macrophage-colony stimulating factor and receptor activator of nuclear factor-κB (RANK) ligand. Tartrate resistant acid phosphatase (TRAP) assay and dentine resorption assay were performed to detect OC formation and their resorption capacity, respectively. The mRNA expression of OCs was examined using a micro-array and real time-quantitative polymerase chain reaction to trace the changes during iDC transdifferentiation into OCs. The results demonstrated that γδ T cells significantly inhibited the generation of the TRAP-positive OCs from iDCs and their resorption capacity. The microarray analysis identified decreased expression level of Fos proto-oncogene AP-1 transcription factor subunit (c-Fos), ATPase H(+) transporting V0 subunit d (ATP6V0D2) and cathepsin K when iDCs were co-cultured with γδ T cells. These genes are associated with OC differentiation, indicating that γδ T cells suppressed iDCs osteoclastogenesis by downregulation of the RANK/c-Fos/ATP6V0D2 signaling pathway. The present findings provide novel insights into the interactions between human γδ T cells and iDCs, and demonstrate that γδ T cells are capable of inhibiting OC formation and their activity via downregulation of genes associated with OC differentiation.
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spelling pubmed-61088642018-08-27 Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c-Fos and ATP6V0D2 Zhu, Xiaolin Zeng, Zhiyong Qiu, Dongbiao Chen, Junmin Int J Mol Med Articles Osteoimmunological studies have revealed that T cells exert a powerful impact on the formation and activity of osteoclasts and bone remodeling. Evidence demonstrates that immature dendritic cells (iDCs) are more efficient transdifferentiating into osteoclasts (OCs) than monocytes. However, whether Vγ9Vδ2 T (γδ T) cells stimulate or inhibit iDC transdifferentiation into OCs has never been reported. The aim of the present study was to investigate the effects of γδ T cells on this transdifferentiation process. γδ T cells and iDCs were isolated from the peripheral blood of healthy volunteers separately and were co-cultured with Transwelll inserts, with γδ T cells in the upper chamber and iDCs in the lower chamber. IDCs were treated with macrophage-colony stimulating factor and receptor activator of nuclear factor-κB (RANK) ligand. Tartrate resistant acid phosphatase (TRAP) assay and dentine resorption assay were performed to detect OC formation and their resorption capacity, respectively. The mRNA expression of OCs was examined using a micro-array and real time-quantitative polymerase chain reaction to trace the changes during iDC transdifferentiation into OCs. The results demonstrated that γδ T cells significantly inhibited the generation of the TRAP-positive OCs from iDCs and their resorption capacity. The microarray analysis identified decreased expression level of Fos proto-oncogene AP-1 transcription factor subunit (c-Fos), ATPase H(+) transporting V0 subunit d (ATP6V0D2) and cathepsin K when iDCs were co-cultured with γδ T cells. These genes are associated with OC differentiation, indicating that γδ T cells suppressed iDCs osteoclastogenesis by downregulation of the RANK/c-Fos/ATP6V0D2 signaling pathway. The present findings provide novel insights into the interactions between human γδ T cells and iDCs, and demonstrate that γδ T cells are capable of inhibiting OC formation and their activity via downregulation of genes associated with OC differentiation. D.A. Spandidos 2018-10 2018-07-23 /pmc/articles/PMC6108864/ /pubmed/30066839 http://dx.doi.org/10.3892/ijmm.2018.3791 Text en Copyright: © Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhu, Xiaolin
Zeng, Zhiyong
Qiu, Dongbiao
Chen, Junmin
Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c-Fos and ATP6V0D2
title Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c-Fos and ATP6V0D2
title_full Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c-Fos and ATP6V0D2
title_fullStr Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c-Fos and ATP6V0D2
title_full_unstemmed Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c-Fos and ATP6V0D2
title_short Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c-Fos and ATP6V0D2
title_sort vγ9vδ2 t cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of rank, c-fos and atp6v0d2
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108864/
https://www.ncbi.nlm.nih.gov/pubmed/30066839
http://dx.doi.org/10.3892/ijmm.2018.3791
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