Schmidl, Christian and Hansmann, Leo and Andreesen, Reinhard and Edinger, Matthias and Hoffmann, Petra and Rehli, Michael (2011) Epigenetic reprogramming of the RORC locus during in vitro expansion is a distinctive feature of human memory but not naive Treg. EUROPEAN JOURNAL OF IMMUNOLOGY, 41 (5). pp. 1491-1498. ISSN 0014-2980,
Full text not available from this repository. (Request a copy)Abstract
The adoptive transfer of in vitro expanded Treg is a promising treatment option for autoimmune as well as alloantigen-induced diseases. Yet, concerns about the phenotypic and functional stability of Tregs upon in vitro culture command both careful selection of the starting population and thorough characterization of the final cell product. Recently, a high degree of developmental plasticity has been described for murine Treg and Th17 cells. Similarly, IL-17-producing FOXP3(+) cells have been detected among the CD45RA(-) memorytype subpopulation of human Tregs ex vivo. This prompted us to investigate the predisposition of human naive and memory Tregs to develop into Th17 cells during polyclonal in vitro expansion. Here, we show that stimulation-induced DNA demethylation of RORC, which encodes the lineage-defining transcription factor for Th17 cells, occurs selectively in CD45RA(-) memory-type Tregs, irrespective of their FOXP3 expression level. On the contrary, naive CD45RA(+) Tregs retain stable CpG methylation across the RORC locus even upon prolonged ex vivo expansion and in consequence show only amarginal tendency to express RORC and develop into IL-17-producing cells. These findings are highly relevant for the generation of therapeutic Treg products.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATORY T-CELLS; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; TRANSCRIPTION FACTOR FOXP3; DNA METHYLATION; GAMMA-T; PROINFLAMMATORY IL-17(+); EX-VIVO; DIFFERENTIATION; EXPRESSION; DNA demethylation; RORc enhancer regions; Th17 cells; Treg plasticity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jun 2020 04:54 |
| Last Modified: | 22 Jun 2020 04:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20888 |
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