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Dental follicle mesenchymal stem cells down‐regulate Th2‐mediated immune response in asthmatic patients mononuclear cells
Author(s) -
Genç D.,
Zibandeh N.,
Nain E.,
Gökalp M.,
Özen A. O.,
Göker M. K.,
Akkoç T.
Publication year - 2018
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13126
Subject(s) - foxp3 , mesenchymal stem cell , immunology , peripheral blood mononuclear cell , immune system , t cell , cytokine , medicine , immunotherapy , cancer research , biology , pathology , in vitro , biochemistry
Summary Background Asthma is a chronic inflammatory disease in which inflammatory responses have the polarisation of CD 4 + T cells to Th2 cells. Dental follicle mesenchymal stem cells ( DFSC s) have strong anti‐inflammatory properties comparable to other mesenchymal stem cells. Objective We investigated the immunomodulatory effects of DFSC s on CD 4 + 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‐ CD 3/anti‐ CD 28 mA bs, Der p1 or IFN ‐γ in the presence and absence of DFSC s and analysed for T cell viability and proliferation, CD 4 + CD 25 + FOXP 3 + regulatory T cell frequencies, cytokine expression, and GATA 3, T bet and FoxP3 expressions. Neutralisation of TGF ‐β and blockade of IDO and PGE 2 pathways were performed to determine suppressive signalling pathways of DFSC s. Results Dental follicle mesenchymal stem cells suppressed proliferative responses of CD 4 + T lymphocytes and increased the frequency of Treg cells. DFSC s decreased effector and effector memory CD 4 + T cell phenotypes in favour of naïve T cell markers. DFSC s decreased IL ‐4 and GATA 3 expression and increased IFN ‐γ, T‐bet and IL ‐10 expression in asthmatics. Costimulatory molecules were suppressed in monocytes with DFSC s in the cocultures. DFSC s 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.