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Human gingiva tissue-derived MSC ameliorates immune-mediated bone marrow failure of aplastic anemia via suppression of Th1 and Th17 cells and enhancement of CD4+Foxp3+ regulatory T cells differentiation.

ABSTRACT: Accumulating evidence has revealed that human gingiva-derived mesenchymal stem cells (GMSCs) are emerging as a new line of mesenchymal stem cells and may have the potential to control or even treat autoimmune diseases through maintaining the balance between Th and Treg cells. Given that GMSCs have a robust immune regulatory function and regenerative ability, we investigated the effect of GMSCs on preventing T cell-mediated bone marrow failure (BMF) in a mouse model. We observed that GMSCs markedly improved mice survival and attenuated histological bone marrow (BM) damage. Moreover, we found GMSCs significantly reduced cell infiltration of CD8+ cells, Th1 and Th17 cells, whereas increased CD4+Foxp3+ regulatory T cells (Tregs) differentiation in lymph nodes. GMSCs also suppressed the levels of TNF-?, IFN-?, IL-17A and IL-6, but IL-10 was increased in serum. The live in vivo imaging identified that GMSCs can home into inflammatory location on BM. Our results demonstrate that GMSCs attenuate T cell-mediated BMF through regulating the balance of Th1, Th17 and Tregs, implicating that application of GMSCs may provide a promising approach in prevention and treatment of patients with aplastic anemia.

SUBMITTER: Zhao J

PROVIDER: S-EPMC6943455 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Human gingiva tissue-derived MSC ameliorates immune-mediated bone marrow failure of aplastic anemia <i>via</i> suppression of Th1 and Th17 cells and enhancement of CD4+Foxp3+ regulatory T cells differentiation.

Zhao Jianzhi J Chen Jingrong J Huang Feng F Wang Julie J Su Wenru W Zhou Jianyao J Qi Quanyin Q Cao Fenglin F Sun Baoqing B Liu Zhongmin Z Bellanti Joseph A JA Zheng Songguo S

American journal of translational research 20191215 12

Accumulating evidence has revealed that human gingiva-derived mesenchymal stem cells (GMSCs) are emerging as a new line of mesenchymal stem cells and may have the potential to control or even treat autoimmune diseases through maintaining the balance between Th and Treg cells. Given that GMSCs have a robust immune regulatory function and regenerative ability, we investigated the effect of GMSCs on preventing T cell-mediated bone marrow failure (BMF) in a mouse model. We observed that GMSCs marked ...[more]

PMID: 31934306

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Project description:Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor suppressing immune and inflammatory responses. We assessed the anti-inflammatory effects of Apremilast in type II collagen (CII)-induced arthritis (CIA) mouse model. To determine whether Apremilast can ameliorate arthritis onset in this model, Apremilast was given orally at day 14 after CII immunization. Bone erosion was measured by histological and micro-computed tomographic analysis. Anti-mouse CII antibody levels were measured by enzyme-linked immunosorbent assay, and Th17, Th1 cells, and CD4+Foxp3+ regulatory T (Treg) cells were assessed by flow cytometry in the lymph nodes. Human cartilage and rheumatoid arthritis (RA) synovial fibroblasts (RASFs) implantation in the severe combined immunodeficiency mouse model of RA were used to study the role of Apremilast in the suppression of RASF-mediated cartilage destruction in vivo. Compared with untreated and vehicle control groups, we found that Apremilast therapy delayed arthritis onset and reduced arthritis scores in the CIA model. Total serum IgG, IgG1, IgG2a, and IgG2b were all decreased in the Apremilast treatment groups. Moreover, Apremilast markedly prevented the development of bone erosions in CIA mice by CT analysis. Furthermore, in the Apremilast treated group, the frequency of Th17 cells and Th1 cells was significantly decreased while Treg cells' frequency was significantly increased. The high dose of Apremilast (25 mg/kg) was superior to low dose (5 mg/kg) in treating CIA. Apremilast treatment reduced the migratory ability of RASFs and their destructive effect on cartilage. Compared with the model group, Apremilast treatment significantly reduced the RASFs invasion cartilage scores in both primary implant and contralateral implant models. Our data suggest that Apremilast is effective in treating autoimmune arthritis and preventing the bone erosion in the CIA model, implicating its therapeutic potential in patients with RA.

Dataset Information

Human gingiva tissue-derived MSC ameliorates immune-mediated bone marrow failure of aplastic anemia via suppression of Th1 and Th17 cells and enhancement of CD4+Foxp3+ regulatory T cells differentiation.

Publications

Human gingiva tissue-derived MSC ameliorates immune-mediated bone marrow failure of aplastic anemia <i>via</i> suppression of Th1 and Th17 cells and enhancement of CD4+Foxp3+ regulatory T cells differentiation.

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