Lkb1 in dendritic cells restricts CD8+Foxp3+regulatory T cells expansion in vivo

Abstract

Liver kinase B1 (Lkb1) in dendritic cells (DCs) plays a key role in maintaining immunity homeostasis and adaptive immunity by controlling the CD4⁺Foxp3⁺T regulatory cell (CD4⁺Tregs) pool and T cells activation. However, the function of Lkb1 in DCs for the regulation of CD8⁺Foxp3⁺T regulatory cells (CD8⁺Tregs) has not been addressed. Herein, we found that Lkb1-deficient DCs could lead to excessive CD8⁺Tregs expansion in multiple organs. We found that OX40 expression was significantly higher in Lkb1-deficient DCs compared with that in wild-type (WT) mice, suggesting a potential pathway of CD8⁺Treg expansion. Moreover, we found that CD8⁺Tregs from mice with conditional deletion Lkb1 in DCs (KO) displayed an activated phenotype and expressed higher levels of specific markers, including ICOS and CD103. Interestingly, compared with the WT mice without lipopolysaccharide(LPS) treatment, we found that CD8⁺Tregs population increased in the WT mice with LPS treatment which can selectively delete Lkb1 protein in DCs. However, there was no significant difference in CD8⁺Tregs population in the KO mice between LPS treatment group and non-LPS treatment. Collectively, our findings identified Lkb1 in DCs as a crucial regulator of CD8⁺Treg expansion.

Keywords: CD8(+)Tregs; Dendritic cells; Lkb1; OX40/OX40L.