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:
- Creative Commons
- Differential regulation of Effector and Regulatory T cell function by Blimp1.
- Authors: Bankoti R, Ogawa C, Nguyen T, Emadi L, Couse M, Salehi S, Fan X, Dhall D, Wang Y, Brown J, Funari V, Tang J, Martins GA
- Issue date: 2017 Sep 21
- Dysregulated follicular regulatory T cells and antibody responses exacerbate experimental autoimmune encephalomyelitis.
- Authors: Luo L, Hu X, Dixon ML, Pope BJ, Leavenworth JD, Raman C, Meador WR, Leavenworth JW
- Issue date: 2021 Jan 19
- Cutting Edge: CRISPR-Based Transcriptional Regulators Reveal Transcription-Dependent Establishment of Epigenetic Memory of <i>Foxp3</i> in Regulatory T Cells.
- Authors: Cameron J, Martino P, Nguyen L, Li X
- Issue date: 2020 Dec 1
- Epigenetic mechanisms of regulation of Foxp3 expression.
- Authors: Lal G, Bromberg JS
- Issue date: 2009 Oct 29
- 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