Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation.
Document with supplemental ...
Open Access publication with ...
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Palam, Lakshmi Reddy
Kaplan, Mark H
MetadataShow full item record
AbstractSummary Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. Here, we establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway is dependent on the transcriptional regulator Blimp1, which prevents downregulation of Foxp3 expression and “toxic” gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulates IL-6- and STAT3-dependent Dnmt3a expression and function restraining methylation of Treg cell-specific conserved non-coding sequence 2 (CNS2) in the Foxp3 locus. Consequently, CNS2 is heavily methylated when Blimp1 is ablated, leading to a loss of Foxp3 expression and severe disease. These findings identify a Blimp1-dependent pathway that preserves Treg cell stability in inflamed non-lymphoid tissues.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
PublisherElsevier (Cell Press)
The following license files are associated with this item:
- Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus.
- Authors: Feng Y, Arvey A, Chinen T, van der Veeken J, Gasteiger G, Rudensky AY
- Issue date: 2014 Aug 14
- TNF receptor 2 signaling prevents DNA methylation at the <i>Foxp3</i> promoter and prevents pathogenic conversion of regulatory T cells.
- Authors: Tseng WY, Huang YS, Clanchy F, McNamee K, Perocheau D, Ogbechi J, Luo SF, Feldmann M, McCann FE, Williams RO
- Issue date: 2019 Oct 22
- Lkb1 maintains T<sub>reg</sub> cell lineage identity.
- Authors: Wu D, Luo Y, Guo W, Niu Q, Xue T, Yang F, Sun X, Chen S, Liu Y, Liu J, Sun Z, Zhao C, Huang H, Liao F, Han Z, Zhou D, Yang Y, Xu G, Cheng T, Feng X
- Issue date: 2017 Jun 16
- Self-antigen-driven activation induces instability of regulatory T cells during an inflammatory autoimmune response.
- Authors: Bailey-Bucktrout SL, Martinez-Llordella M, Zhou X, Anthony B, Rosenthal W, Luche H, Fehling HJ, Bluestone JA
- Issue date: 2013 Nov 14
- TGF-β-mediated Foxp3 gene expression is cooperatively regulated by Stat5, Creb, and AP-1 through CNS2.
- Authors: Ogawa C, Tone Y, Tsuda M, Peter C, Waldmann H, Tone M
- Issue date: 2014 Jan 1