IFN-γ stimulation of dental follicle mesenchymal stem cells modulates immune response of CD4+ T lymphocytes in Der p1+ asthmatic patients in vitro

ABSTRACT

Background: House dust mite (Dermataphagoides pteronyssinus) is a widespread risk factor in the development of asthma. CD4+ T lymphocytes have an important role in the pathogenesis of allergic asthma by polarizing to Th2 cells. Objective: We aimed to evaluate the immunoregulatory effects of dental follicle mesenchymal stem cells with and without IFN-γ stimulation on peripheral blood mononuclear cells of house dust mite sensitive asthmatic patients, and compared those with Dexamethasone as a systemic steroid. Material and methods: PBMC of asthmatic patients and healthy individuals separately cultured with or without DF-MSCs in the presence and absence of IFN-γ or Der p1 or Dexamethasone for 72h. CD4+ T proliferation, cell viability, CD4+CD25+FoxP3+ Treg cell frequency and cytokine profiles of PBMC were evaluated via flow cytometry. Results: DF-MSCs suppressed proliferation of CD4+ T lymphocytes (pCDmix < 0.01, pDerp1 < 0.01, pIFN < 0.005) by increasing the number of FoxP3 expressing CD4 + CD25 + T regulatory cells (pCDmix < 0.005, pDerp1 < 0.01, pIFN < 0.001) and suppressed lymphocyte apoptosis (pCDmix < 0.05, pDerp1< 0.05, pIFN < 0.05), while Dexamethasone increased the apoptosis and decreased Treg cell frequency in asthmatic patients. IFN-γ stimulation increased the suppressive effect of DF-MSCs and also enhanced the frequency of FoxP3 expressing CD4+CD25 + T regulatory cells. The cytokine levels were regulated by DF-MSCs by reducing IL-4 cytokine levels (pCDmix < 0.01, pDerp1 < 0.05, pIFN < 0.05) and upregulating IFN-γ levels (pCDmix < 0.01, pDerp1< 0.05, pIFN < 0.005) in asthmatic patients. Conclusion: IFN-γ stimulated DF-MSCs were found to have a high modulatory effect on CD4 + T cell responses, while Dexamethasone had an apoptotic effect on CD4+ T cells in asthmatic patients. DF-MSCs may be a new cell-based therapy option for allergic diseases including asthma

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