Akkoç T. (Yürütücü)
Yükseköğretim Kurumları Destekli Proje, 2016 - 2018
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