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

<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Asthma is a chronic inflammatory disease in which inflammatory responses have the polarisation of <jats:styled-content style="fixed-case">CD</jats:styled-content>4<jats:sup>+</jats:sup> T cells to Th2 cells. Dental follicle mesenchymal stem cells (<jats:styled-content style="fixed-case">DFSC</jats:styled-content>s) have strong anti‐inflammatory properties comparable to other mesenchymal stem cells.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>We investigated the immunomodulatory effects of <jats:styled-content style="fixed-case">DFSC</jats:styled-content>s on <jats:styled-content style="fixed-case">CD</jats:styled-content>4<jats:sup>+</jats:sup> T helper cell responses of asthmatic patients and compared the results with those obtained with asthmatic subjects on immunotherapy and with healthy individuals.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>Peripheral blood mononuclear cells (<jats:styled-content style="fixed-case">PBMC</jats:styled-content>) were isolated from immunotherapy naïve asthmatics, asthmatics on subcutaneous Der p1 immunotherapy and from healthy individuals. <jats:styled-content style="fixed-case">PBMC</jats:styled-content> were pre‐conditioned with anti‐<jats:styled-content style="fixed-case">CD</jats:styled-content>3/anti‐<jats:styled-content style="fixed-case">CD</jats:styled-content>28 <jats:styled-content style="fixed-case">mA</jats:styled-content>bs, Der p1 or <jats:styled-content style="fixed-case">IFN</jats:styled-content>‐γ in the presence and absence of <jats:styled-content style="fixed-case">DFSC</jats:styled-content>s and analysed for T cell viability and proliferation, <jats:styled-content style="fixed-case">CD</jats:styled-content>4<jats:sup>+</jats:sup><jats:styled-content style="fixed-case">CD</jats:styled-content>25<jats:sup>+</jats:sup><jats:styled-content style="fixed-case">FOXP</jats:styled-content>3<jats:sup>+</jats:sup> regulatory T cell frequencies, cytokine expression, and <jats:styled-content style="fixed-case">GATA</jats:styled-content>3, T bet and FoxP3 expressions. Neutralisation of <jats:styled-content style="fixed-case">TGF</jats:styled-content>‐β and blockade of <jats:styled-content style="fixed-case">IDO</jats:styled-content> and <jats:styled-content style="fixed-case">PGE</jats:styled-content>2 pathways were performed to determine suppressive signalling pathways of <jats:styled-content style="fixed-case">DFSC</jats:styled-content>s.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Dental follicle mesenchymal stem cells suppressed proliferative responses of <jats:styled-content style="fixed-case">CD</jats:styled-content>4<jats:sup>+</jats:sup> T lymphocytes and increased the frequency of Treg cells. <jats:styled-content style="fixed-case">DFSC</jats:styled-content>s decreased effector and effector memory <jats:styled-content style="fixed-case">CD</jats:styled-content>4<jats:sup>+</jats:sup> T cell phenotypes in favour of naïve T cell markers. <jats:styled-content style="fixed-case">DFSC</jats:styled-content>s decreased <jats:styled-content style="fixed-case">IL</jats:styled-content>‐4 and <jats:styled-content style="fixed-case">GATA</jats:styled-content>3 expression and increased <jats:styled-content style="fixed-case">IFN</jats:styled-content>‐γ, T‐bet and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10 expression in asthmatics. Costimulatory molecules were suppressed in monocytes with <jats:styled-content style="fixed-case">DFSC</jats:styled-content>s in the cocultures. <jats:styled-content style="fixed-case">DFSC</jats:styled-content>s down‐regulated inflammatory responses via <jats:styled-content style="fixed-case">IDO</jats:styled-content> and <jats:styled-content style="fixed-case">TGF</jats:styled-content>‐β pathways in asthmatic patients.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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 <jats:styled-content style="fixed-case">DFSC</jats:styled-content>‐based cell therapy may provide pro‐tolerogenic immunomodulation relevant to allergic diseases such as asthma.</jats:p></jats:sec>