Regulatory T (Treg) cells are a distinct T-cell lineage characterized by sustained Foxp3 expression and potent suppressor function, but the upstream dominant factors that preserve Treg lineage-specific features are mostly unknown. Here, we show that Lkb1 maintains Treg cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor (TCR) stimulation Lkb1 protein expression is upregulated in Treg cells but not in conventional T cells. Mice with Treg cell-specific deletion of Lkb1 develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most Treg 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 Treg cell lineage identity.

The adsorption of poly(4-vinyl pyridine) (P4VP) unimers into spherical core-shell micelles self-assembled by polystyrene-block-poly(acrylic acid) in ethanol is studied by a combination of static light scattering (SLS) and dynamic light scattering (DLS). P4VP unimers with a coil size of ca. 7.9 nm can be first absorbed into the PS-b-PAA spherical core-shell micelles with a hydrodynamic diameter of 79.9 nm and then penetrate into the shell of the micelles to form hydrogen-bonded micelleunimers complexes in ethanol. During the adsorption, the hydrodynamic diameter and gyration radius of the micelle-unimers complexes decrease first and then stay almost unchanged when P4VP solution in ethanol is added into the PS-b-PAA micelle solution. It is also found that the structure of the micelleunimers complexes remains spherical but becomes smaller and denser than that of the PS-b-PAA micelles after absorption of P4VP unimers.

To balance immunity and tolerance, the endogenous pool of Foxp3+ regulatory T (Treg) cells is tightly controlled, but the underlying mechanisms of this control remain poorly understood. Here we show that the number of Treg cells is negatively regulated by the kinase Lkb1 in dendritic cells (DCs). Conditional knockout of the Lkb1 gene in DCs leads to excessive Treg cell expansion in multiple organs and dampens antigen-specific T cell immunity. Lkb1-deficient DCs are capable of enhancing, compared with wild-type DCs, Treg cell proliferation via cell-cell contact involving the IKK/IKBα-independent activation of the NF-κB/OX40L pathway. Intriguingly, treating wild-type mice with lipopolysaccharide selectively depletes Lkb1 protein in DCs, resulting in Treg cell expansion and suppressed inflammatory injury upon subsequent challenge. Loss of Lkb1 does not obviously upregulate proinflammatory molecules expression on DCs. We thus identify Lkb1 as a regulatory switch in DCs for controlling Treg cell homeostasis, immune response and tolerance.