V?9V?2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c?Fos and ATP6V0D2.

ABSTRACT: 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?9V?2 T (?? 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 ?? T cells on this transdifferentiation process. ?? T cells and iDCs were isolated from the peripheral blood of healthy volunteers separately and were co?cultured with Transwelll inserts, with ?? 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??B (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 microarray and real time?quantitative polymerase chain reaction to trace the changes during iDC transdifferentiation into OCs. The results demonstrated that ?? 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 ?? T cells. These genes are associated with OC differentiation, indicating that ?? 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 ?? T cells and iDCs, and demonstrate that ?? T cells are capable of inhibiting OC formation and their activity via downregulation of genes associated with OC differentiation.

SUBMITTER: Zhu X 

PROVIDER: S-EPMC6108864 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature