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

Wang,Gaoyuan; Zhang,Junqiang; Fang,Yuan; Cao,Wei; Xu,Bin; Chen,Xiaoyu

doi:10.3892/etm.2018.7036

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

Authors:
- Gaoyuan Wang
- Junqiang Zhang
- Yuan Fang
- Wei Cao
- Bin Xu
- Xiaoyu Chen
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Affiliations: Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230031, P.R. China, Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Blood Transfusion, Anhui No. 2 Provincial People's Hospital, Hefei, Anhui 230041, P.R. China, Department of Histology and Embryology, Anhui Medical University, Hefei, Anhui 230032, P.R. China
Published online on: November 30, 2018 https://doi.org/10.3892/etm.2018.7036
Pages: 679-688
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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