Dental Folikül Kaynaklı Mezenkimal Kök Hücrelerin (DF-MKH) Ev Tozuna Duyarlı Astım Hastalarından Elde Edilen Naive T Lenfositlerin in vitro Th1 ve Th2 Farklılaşması Üzerine Etkisi


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Akkoç T. (Yürütücü)

Yükseköğretim Kurumları Destekli Proje, 2016 - 2018

  • Proje Türü: Yükseköğretim Kurumları Destekli Proje
  • Başlama Tarihi: Ağustos 2016
  • Bitiş Tarihi: Mart 2018

Proje Özeti

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 na€ıve asthmatics, asthmatics on subcutaneous Der p1 immunotherapy and from healthy individuals. PBMC were pre-conditioned with anti-CD3/antiCD28 mAbs, Der p1 or IFN-c 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-b 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 na€ıve T cell markers. DFSCs decreased IL-4 and GATA3 expression and increased IFN-c, 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-b 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 prov