Control of T(reg) cell homeostasis and immune equilibrium by Lkb1 in dendritic cells

To balance immunity and tolerance, the endogenous pool of Foxp3(+) regulatory T (T(reg)) cells is tightly controlled, but the underlying mechanisms of this control remain poorly understood. Here we show that the number of T(reg) cells is negatively regulated by the kinase Lkb1 in dendritic cells (DCs). Conditional knockout of the Lkb1 gene in DCs leads to excessive T(reg) cell expansion in multiple organs and dampens antigen-specific T cell immunity. Lkb1-deficient DCs are capable of enhancing, compared with wild-type DCs, T(reg) 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 T(reg) 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 T(reg) cell homeostasis, immune response and tolerance.