Human adipose-tissue derived mesenchymal stem cells induce functional de-novo regulatory T cells with methylated FOXP3 gene DNA
Clinical and Experimental Immunology , Volume 173 - Issue 2 p. 343- 354
Due to their immunomodulatory properties, mesenchymal stem cells (MSC) are interesting candidates for cellular therapy for autoimmune disorders, graft-versus-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+CD25+CD127-forkhead box P3 (FoxP3)+ T cells are functional and whether they originate from effector T cells or represent expanded natural regulatory T cells (nTreg). Perirenal adipose-tissue derived MSC (ASC) obtained from kidney donors induced a 2·1-fold increase in the percentage of CD25+CD127-FoxP3+ cells within the CD4+ T cell population from allostimulated CD25-/dim cells. Interleukin (IL)-2 receptor blocking prevented this induction. The ASC-induced T cells (iTreg) inhibited effector cell proliferation as effectively as nTreg. The vast majority of cells within the iTreg fraction had a methylated FOXP3 gene Treg-specific demethylated region (TSDR) indicating that they were not of nTreg origin. In conclusion, ASC induce Treg from effector T cells. These iTreg have immunosuppressive capacities comparable to those of nTreg. Their induction is IL-2 pathway-dependent. The dual effect of MSC of inhibiting immune cell proliferation while generating de-novo immunosuppressive cells emphasizes their potential as cellular immunotherapeutic agent.
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|Clinical and Experimental Immunology|
|Organisation||Department of Internal Medicine|
Engela, A.U, Hoogduijn, M.J, Boer, K, Litjens, N.H.R, Betjes, M.G.H, Weimar, W, & Baan, C.C. (2013). Human adipose-tissue derived mesenchymal stem cells induce functional de-novo regulatory T cells with methylated FOXP3 gene DNA. Clinical and Experimental Immunology, 173(2), 343–354. doi:10.1111/cei.12120