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- Publisher Website: 10.1084/jem.20102683
- Scopus: eid_2-s2.0-80555139651
- PMID: 21875956
- WOS: WOS:000295318900013
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Article: Critical role of Bcl11b in suppressor function of T regulatory cells and prevention of inflammatory bowel disease
Title | Critical role of Bcl11b in suppressor function of T regulatory cells and prevention of inflammatory bowel disease |
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Authors | |
Issue Date | 2011 |
Citation | Journal of Experimental Medicine, 2011, v. 208, n. 10, p. 2069-2081 How to Cite? |
Abstract | Dysregulated CD4 + T cell responses and alterations in T regulatory cells (T reg cells) play a critical role in autoimmune diseases, including inflammatory bowel disease (IBD). The current study demonstrates that removal of Bcl11b at the double-positive stage of T cell development or only in T reg cells causes IBD because of proinflammatory cytokine-producing CD4 + T cells infiltrating the colon. Provision of WT T reg cells prevented IBD, demonstrating that alterations in T reg cells are responsible for the disease. Furthermore, Bcl11b-deficient T reg cells had reduced suppressor activity with altered gene expression profiles, including reduced expression of the genes encoding Foxp3 and IL-10, and up-regulation of genes encoding proinflammatory cytokines. Additionally, the absence of Bcl11b altered the induction of Foxp3 expression and reduced the generation of induced T reg cells (iT reg cells) after Tgf-β treatment of conventional CD4 + T cells. Bcl11b bound to Foxp3 and IL-10 promoters, as well as to critical conserved noncoding sequences within the Foxp3 and IL-10 loci, and mutating the Bcl11b binding site in the Foxp3 promoter reduced expression of a luciferase reporter gene. These experiments demonstrate that Bcl11b is indispensable for T reg suppressor function and for maintenance of optimal Foxp3 and IL-10 gene expression, as well as for the induction of Foxp3 expression in conventional CD4 + T cells in response to Tgf-β and generation of iT reg cells. © 2011 VanValkenburgh et al. |
Persistent Identifier | http://hdl.handle.net/10722/249054 |
ISSN | 2023 Impact Factor: 12.6 2023 SCImago Journal Rankings: 6.838 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | VanValkenburgh, Jeffrey | - |
dc.contributor.author | Albu, Diana I. | - |
dc.contributor.author | Bapanpally, Chandra | - |
dc.contributor.author | Casanova, Sarah | - |
dc.contributor.author | Califano, Danielle | - |
dc.contributor.author | Jones, David M. | - |
dc.contributor.author | Ignatowicz, Leszek | - |
dc.contributor.author | Kawamoto, Shimpei | - |
dc.contributor.author | Fagarasan, Sidonia | - |
dc.contributor.author | Jenkins, Nancy A. | - |
dc.contributor.author | Copeland, Neal G. | - |
dc.contributor.author | Liu, Pentao | - |
dc.contributor.author | Avram, Dorina | - |
dc.date.accessioned | 2017-10-27T05:58:59Z | - |
dc.date.available | 2017-10-27T05:58:59Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Journal of Experimental Medicine, 2011, v. 208, n. 10, p. 2069-2081 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | http://hdl.handle.net/10722/249054 | - |
dc.description.abstract | Dysregulated CD4 + T cell responses and alterations in T regulatory cells (T reg cells) play a critical role in autoimmune diseases, including inflammatory bowel disease (IBD). The current study demonstrates that removal of Bcl11b at the double-positive stage of T cell development or only in T reg cells causes IBD because of proinflammatory cytokine-producing CD4 + T cells infiltrating the colon. Provision of WT T reg cells prevented IBD, demonstrating that alterations in T reg cells are responsible for the disease. Furthermore, Bcl11b-deficient T reg cells had reduced suppressor activity with altered gene expression profiles, including reduced expression of the genes encoding Foxp3 and IL-10, and up-regulation of genes encoding proinflammatory cytokines. Additionally, the absence of Bcl11b altered the induction of Foxp3 expression and reduced the generation of induced T reg cells (iT reg cells) after Tgf-β treatment of conventional CD4 + T cells. Bcl11b bound to Foxp3 and IL-10 promoters, as well as to critical conserved noncoding sequences within the Foxp3 and IL-10 loci, and mutating the Bcl11b binding site in the Foxp3 promoter reduced expression of a luciferase reporter gene. These experiments demonstrate that Bcl11b is indispensable for T reg suppressor function and for maintenance of optimal Foxp3 and IL-10 gene expression, as well as for the induction of Foxp3 expression in conventional CD4 + T cells in response to Tgf-β and generation of iT reg cells. © 2011 VanValkenburgh et al. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Experimental Medicine | - |
dc.title | Critical role of Bcl11b in suppressor function of T regulatory cells and prevention of inflammatory bowel disease | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1084/jem.20102683 | - |
dc.identifier.pmid | 21875956 | - |
dc.identifier.scopus | eid_2-s2.0-80555139651 | - |
dc.identifier.volume | 208 | - |
dc.identifier.issue | 10 | - |
dc.identifier.spage | 2069 | - |
dc.identifier.epage | 2081 | - |
dc.identifier.eissn | 1540-9538 | - |
dc.identifier.isi | WOS:000295318900013 | - |
dc.identifier.issnl | 0022-1007 | - |