Control of Treg cell homeostasis and immune equilibrium by Lkb1 in dendritic cells

Nat Commun. 2018 Dec 13;9(1):5298. doi: 10.1038/s41467-018-07545-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Apoptosis / immunology
  • Cell Proliferation / genetics*
  • Dendritic Cells / immunology*
  • Gene Knockout Techniques
  • Homeostasis / physiology
  • I-kappa B Kinase / metabolism
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, SCID
  • OX40 Ligand
  • Protein Serine-Threonine Kinases / genetics*
  • Receptors, OX40 / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Necrosis Factors / metabolism


  • Membrane Glycoproteins
  • OX40 Ligand
  • Receptors, OX40
  • Tnfrsf4 protein, mouse
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factors
  • Protein Serine-Threonine Kinases
  • Stk11 protein, mouse
  • I-kappa B Kinase
  • AMP-Activated Protein Kinases