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Stimulation of tolerogenic dendritic cells using dexamethasone and 1,25-dihydroxyvitamin D3 represses autologous T cell activation and chondrocyte inflammation.

Abstract：

:Human osteoarthritis (OA) has been reclassified as a systemic musculoskeletal disorder involving activation of the innate and adaptive immune systems. Elevated pro-inflammatory cytokines may serve a key function in the development of the disease. 1,25-Dihydroxyvitamin D3 and dexamethasone (vitD3/Dex) may inhibit inflammation by acting on tolerogenic dendritic cells (tolDCs) in chronic inflammatory conditions. In the present study, DCs were isolated from peripheral blood mononuclear cells of patients with OA. DCs expressing high levels of co-stimulatory molecules maintain a tolerogenic phenotype under stimulation with LPS, which promotes DC maturation to generate tolDCs. When vitD3/Dex were added in the current study, the tolDCs produced pro-inflammatory cytokines, including low levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-10, and high levels of transforming growth factor-β. However, when vitD3/Dex were added to DCs without LPS stimulation, the levels of IL-10 were high. DCs with LPS stimulation increased the percentage of T-cells that produced IFN-γ and IL-17 and DCs with vitD3/Dex treatment alone increased the percentage of T-cells that produced IL-10 and FoxP3. However, those cytokines decrease in DCs co-processed with LPS and vitD3/Dex. The IL-10 release by the stimulated T cells was indicated to repress autologous T cell proliferation via soluble IL-10 and cell-cell contact. Furthermore, tolDCs and regulatory T cells suppressed matrix metalloproteinase (MMP)-1 and MMP-13 secretion by chondrocytes. Additionally, Akt and p38 mitogen-activated protein kinase signaling were demonstrated to be involved in the regulatory effects of Dec and vitD3 in DCs. The present findings suggest a novel mechanism underlying the beneficial effects of tolDCs, particularly in association with the pathogenesis of OA.

journal_name

Exp Ther Med

journal_title

Experimental and therapeutic medicine

authors

Wang G,Zhang J,Fang Y,Cao W,Xu B,Chen X

doi

10.3892/etm.2018.7036

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

679-688

issue

eissn

1792-0981

issn

1792-1015

pii

ETM-0-0-7036

journal_volume

pub_type

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Stimulation of tolerogenic dendritic cells using dexamethasone and 1,25-dihydroxyvitamin D3 represses autologous T cell activation and chondrocyte inflammation.