Lkb1 maintains T<sub>reg</sub> cell lineage identity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28621313.
- Also identified by DOI 10.1038/ncomms15876 and PMC identifier 5481770.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Regulatory T (T<sub>reg</sub>) cells are a distinct T-cell lineage characterized by sustained Foxp3 expression and potent suppressor function, but the upstream dominant factors that preserve T<sub>reg</sub> lineage-specific features are mostly unknown. Here, we show that Lkb1 maintains T<sub>reg</sub> cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor (TCR) stimulation Lkb1 protein expression is upregulated in T<sub>reg</sub> cells but not in conventional T cells. Mice with T<sub>reg</sub> cell-specific deletion of Lkb1 develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most T<sub>reg</sub> cells. Lkb1 stabilizes Foxp3 expression by preventing STAT4-mediated methylation of the conserved noncoding sequence 2 (CNS2) in the Foxp3 locus. Independent of maintaining Foxp3 expression, Lkb1 programs the expression of a wide spectrum of immunosuppressive genes, through mechanisms involving the augmentation of TGF-β signalling. These findings identify a critical function of Lkb1 in maintaining T<sub>reg</sub> cell lineage identity.
Medical subject headings
- Protein Serine-Threonine Kinases
- T-Lymphocytes, Regulatory