Human adipose‐tissue derived mesenchymal stem cells induce functional de‐novo regulatory T cells with methylated FOXP3 gene DNA. (4th July 2013)

• Record Type: Journal Article
• Authors: Engela, A. U.; Hoogduijn, M. J.; Boer, K.; Litjens, N. H. R.; Betjes, M. G. H.; Weimar, W.; Baan, C. C.
• Is Part Of: Clinical and experimental immunology. Volume 173:Number 2(2013:Aug.)
• Page Start: 343
• Page End: 354
• Publication Date: 2013-07-04
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12120
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Due to their immunomodulatory properties, mesenchymal stem cells (MSC) are interesting candidates for cellular therapy for autoimmune disorders, graft‐<italic>versus</italic>‐host disease and allograft rejection. MSC inhibit the proliferation of effector T cells and induce T cells with a regulatory phenotype. So far it is unknown whether human MSC‐induced CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>–</sup>forkhead box P3 (FoxP3)<sup>+</sup> T cells are functional and whether they originate from effector T cells or represent expanded natural regulatory T cells (nT<sub>reg</sub>). Perirenal adipose‐tissue derived MSC (ASC) obtained from kidney donors induced a 2·1‐fold increase in the percentage of CD25<sup>+</sup>CD127<sup>–</sup>FoxP3<sup>+</sup> cells within the CD4<sup>+</sup> T cell population from allostimulated CD25<sup>–/dim</sup> cells. Interleukin (IL)‐2 receptor blocking prevented this induction. The ASC‐induced T cells (iT<sub>reg</sub>) inhibited effector cell proliferation as effectively as nT<sub>reg</sub>. The vast majority of cells within the iTreg fraction had a methylated <italic>FOXP3</italic> gene Treg‐specific demethylated region (TSDR) indicating that they were not of nT<sub>reg</sub> origin. In conclusion, ASC induce T<sub>reg</sub> from effector T cells. These iT<sub>reg</sub> have immunosuppressive capacities comparable to those of nT<sub>reg</sub>. Their induction is IL‐2 pathway‐dependent. The dual effect of MSC of inhibiting immune cell proliferation while generating <italic>de‐novo</italic> immunosuppressive cells emphasizes their potential as cellular immunotherapeutic agent.</p> </abstract>