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Inicio Allergologia et Immunopathologia IFN-γ stimulation of dental follicle mesenchymal stem cells modulates immune re...
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Vol. 47. Issue 5.
Pages 467-476 (September - October 2019)
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Vol. 47. Issue 5.
Pages 467-476 (September - October 2019)
Original Article
DOI: 10.1016/j.aller.2018.12.005
IFN-γ stimulation of dental follicle mesenchymal stem cells modulates immune response of CD4+ T lymphocytes in Der p1+ asthmatic patients in vitro
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D. Gença, N. Zibandeha, E. Nainb, Ü. Arığa, K. Gökerc, E.K. Aydınerb, T. Akkoça,*
a Marmara University Faculty of Medicine Department of Pediatric Allergy and Immunology, Istanbul, Turkey
b Marmara University Training and Research Hospital, Department of Pediatric Allergy and Immunology, Istanbul, Turkey
c Marmara University Faculty of Dentistry Department of Maxillofacial Surgery, Istanbul, Turkey
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Table 1. Demographic data. Asthmatic patients were clinically inspected and evaluated for asthma symptoms. Skin prick test (SPT), forced expiratory volume (FEV%), and serum IgE levels were recorded for patient selection criteria. A: asthmatic patients; C: healthy subjects.
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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.

Keywords:
Dental follicle mesenchymal stem cells
Asthma
House dust mite
Der p1

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