Hansmann, Leo and Schmidl, Christian and Kett, Janina and Steger, Lena and Andreesen, Reinhard and Hoffmann, Petra and Rehli, Michael and Edinger, Matthias (2012) Dominant Th2 Differentiation of Human Regulatory T Cells upon Loss of FOXP3 Expression. JOURNAL OF IMMUNOLOGY, 188 (3). pp. 1275-1282. ISSN 0022-1767,
Full text not available from this repository. (Request a copy)Abstract
CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) are pivotal for peripheral self-tolerance. They prevent immune responses to auto- and alloantigens and are thus under close scrutiny as cellular therapeutics for autoimmune diseases and the prevention or treatment of alloresponses after organ or stem cell transplantation. We previously showed that human Treg with a memory cell phenotype, but not those with a naive phenotype, rapidly downregulate expression of the lineage-defining transcription factor FOXP3 upon in vitro expansion. We now compared the transcriptomes of stable FOXP3(+) Treg and converted FOXP3(-) ex-Treg by applying a newly developed intranuclear staining protocol that permits the isolation of intact mRNA from fixed, permeabilized, and FACS-purified cell populations. Whole-genome microarray analysis revealed strong and selective upregulation of Th2 signature genes, including GATA-3, IL-4, IL-5, and IL-13, upon downregulation of FOXP3. Th2 differentiation of converted FOXP3(-) ex-Treg occurred even under nonpolarizing conditions and could not be prevented by IL-4 signaling blockade. Thus, our studies identify Th2 differentiation as the default developmental program of human Treg after downregulation of FOXP3. The Journal of Immunology, 2012, 188: 1275-1282.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; IN-VITRO EXPANSION; EX-VIVO; TRANSCRIPTION FACTORS; FATE DETERMINATION; DNA METHYLATION; GENE-EXPRESSION; CUTTING EDGE; TH17 CELLS; |
| 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 May 2020 04:53 |
| Last Modified: | 22 May 2020 04:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19325 |
Actions (login required)
 |
View Item |
