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

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, CD4CD25FoxP3 Treg cell frequency and cytokine profiles of PBMC were evaluated via flow cytometry.

Results: DF-MSCs suppressed proliferation of CD4 T lymphocytes (p<0.01, p<0.01, p<0.005) by increasing the number of FoxP3 expressing CD4CD25 T regulatory cells (p<0.005, p<0.01, p<0.001) and suppressed lymphocyte apoptosis (p<0.05, p<0.05, p<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 CD4CD25 T regulatory cells. The cytokine levels were regulated by DF-MSCs by reducing IL-4 cytokine levels (p<0.01, p<0.05, p<0.05) and upregulating IFN-γ levels (p<0.01, p<0.05, p<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.