LKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways

The present study has examined the role of the serine/threonine kinase LKB1 in the survival and differentiation of CD4/8 double positive thymocytes. LKB1-null DPs can respond to signals from the mature α/β T-cell-antigen receptor and initiate positive selection. However, in the absence of LKB1, thym...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2013-03, Vol.8 (3), p.e60217-e60217
Main Authors: Zarrouk, Marouan, Rolf, Julia, Cantrell, Doreen Ann
Format: Article
Language:English
Subjects:
AMP
AMP-activated protein kinase
AMP-Activated Protein Kinases - genetics
AMP-Activated Protein Kinases - metabolism
Analysis
Animals
Antigens
B cells
Biology
CD4 antigen
Cells, Cultured
Clonal deletion
Clonal selection
Flow Cytometry
Homeostasis
Immunoblotting
Immunology
Impact analysis
Kinases
Life sciences
LKB1 protein
Lymphocytes
Lymphocytes T
Lymphoid tissue
Lymphopenia
Maturation
Metabolism
Mice
Mice, Mutant Strains
Mutants
Natural killer cells
Pathways
Positive selection
Protein kinases
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Protein-serine/threonine kinase
Proteins
Receptors, Antigen, T-Cell - genetics
Receptors, Antigen, T-Cell - metabolism
Signal Transduction - genetics
Signal Transduction - physiology
Substrates
T cell receptors
T cells
T-cell receptor
Threonine
Thymocytes
Tissues
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The present study has examined the role of the serine/threonine kinase LKB1 in the survival and differentiation of CD4/8 double positive thymocytes. LKB1-null DPs can respond to signals from the mature α/β T-cell-antigen receptor and initiate positive selection. However, in the absence of LKB1, thymocytes fail to mature to conventional single positive cells causing severe lymphopenia in the peripheral lymphoid tissues. LKB1 thus appears to be dispensable for positive selection but important for the maturation of positively selected thymocytes. LKB1 also strikingly prevented the development of invariant Vα14 NKT cells and innate TCR αβ gut lymphocytes. Previous studies with gain of function mutants have suggested that the role of LKB1 in T cell development is mediated by its substrate the AMP-activated protein kinase (AMPK). The present study now analyses the impact of AMPK deletion in DP thymocytes and shows that the role of LKB1 during the development of both conventional and innate T cells is mediated by AMPK-independent pathways.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0060217