Dental follicle mesenchymal stem cells down-regulate Th2-mediated immune response in asthmatic patients mononuclear cells

Clin Exp Allergy. 2018 Jun;48(6):663-678. doi: 10.1111/cea.13126. Epub 2018 Apr 6.

Abstract

Background: Asthma is a chronic inflammatory disease in which inflammatory responses have the polarisation of CD4+ T cells to Th2 cells. Dental follicle mesenchymal stem cells (DFSCs) have strong anti-inflammatory properties comparable to other mesenchymal stem cells.

Objective: We investigated the immunomodulatory effects of DFSCs on CD4+ T helper cell responses of asthmatic patients and compared the results with those obtained with asthmatic subjects on immunotherapy and with healthy individuals.

Method: Peripheral blood mononuclear cells (PBMC) were isolated from immunotherapy naïve asthmatics, asthmatics on subcutaneous Der p1 immunotherapy and from healthy individuals. PBMC were pre-conditioned with anti-CD3/anti-CD28 mAbs, Der p1 or IFN-γ in the presence and absence of DFSCs and analysed for T cell viability and proliferation, CD4+ CD25+ FOXP3+ regulatory T cell frequencies, cytokine expression, and GATA3, T bet and FoxP3 expressions. Neutralisation of TGF-β and blockade of IDO and PGE2 pathways were performed to determine suppressive signalling pathways of DFSCs.

Results: Dental follicle mesenchymal stem cells suppressed proliferative responses of CD4+ T lymphocytes and increased the frequency of Treg cells. DFSCs decreased effector and effector memory CD4+ T cell phenotypes in favour of naïve T cell markers. DFSCs decreased IL-4 and GATA3 expression and increased IFN-γ, T-bet and IL-10 expression in asthmatics. Costimulatory molecules were suppressed in monocytes with DFSCs in the cocultures. DFSCs down-regulated inflammatory responses via IDO and TGF-β pathways in asthmatic patients.

Conclusion: Dental follicle mesenchymal stem cells suppressed allergen-induced Th2-cell polarisation in favour of Th1 responses and attenuated antigen-presenting cell co-stimulatory activities. These studies suggest that DFSC-based cell therapy may provide pro-tolerogenic immunomodulation relevant to allergic diseases such as asthma.

Keywords: asthma; dental follicle mesenchymal stem cells; house dust mite; immunomodulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Apoptosis
  • Asthma / diagnosis
  • Asthma / etiology*
  • Biomarkers
  • Cell Communication*
  • Child
  • Child, Preschool
  • Cytokines / metabolism
  • Dental Sac / cytology*
  • Female
  • Humans
  • Immunomodulation*
  • Immunophenotyping
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism*

Substances

  • Biomarkers
  • Cytokines