Skip to main content

The liver kinase B1 is a central regulator of T cell development, activation, and metabolism.

Publication ,  Journal Article
MacIver, NJ; Blagih, J; Saucillo, DC; Tonelli, L; Griss, T; Rathmell, JC; Jones, RG
Published in: J Immunol
October 15, 2011

T cell activation leads to engagement of cellular metabolic pathways necessary to support cell proliferation and function. However, our understanding of the signal transduction pathways that regulate metabolism and their impact on T cell function remains limited. The liver kinase B1 (LKB1) is a serine/threonine kinase that links cellular metabolism with cell growth and proliferation. In this study, we demonstrate that LKB1 is a critical regulator of T cell development, viability, activation, and metabolism. T cell-specific ablation of the gene that encodes LKB1 resulted in blocked thymocyte development and a reduction in peripheral T cells. LKB1-deficient T cells exhibited defects in cell proliferation and viability and altered glycolytic and lipid metabolism. Interestingly, loss of LKB1 promoted increased T cell activation and inflammatory cytokine production by both CD4(+) and CD8(+) T cells. Activation of the AMP-activated protein kinase (AMPK) was decreased in LKB1-deficient T cells. AMPK was found to mediate a subset of LKB1 functions in T lymphocytes, as mice lacking the α1 subunit of AMPK displayed similar defects in T cell activation, metabolism, and inflammatory cytokine production, but normal T cell development and peripheral T cell homeostasis. LKB1- and AMPKα1-deficient T cells each displayed elevated mammalian target of rapamycin complex 1 signaling and IFN-γ production that could be reversed by rapamycin treatment. Our data highlight a central role for LKB1 in T cell activation, viability, and metabolism and suggest that LKB1-AMPK signaling negatively regulates T cell effector function through regulation of mammalian target of rapamycin activity.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

October 15, 2011

Volume

187

Issue

8

Start / End Page

4187 / 4198

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Protein Serine-Threonine Kinases
  • Mice, Knockout
  • Mice
  • Lymphocyte Activation
  • Immunology
  • Immunoblotting
  • Homeostasis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
MacIver, N. J., Blagih, J., Saucillo, D. C., Tonelli, L., Griss, T., Rathmell, J. C., & Jones, R. G. (2011). The liver kinase B1 is a central regulator of T cell development, activation, and metabolism. J Immunol, 187(8), 4187–4198. https://doi.org/10.4049/jimmunol.1100367
MacIver, Nancie J., Julianna Blagih, Donte C. Saucillo, Luciana Tonelli, Takla Griss, Jeffrey C. Rathmell, and Russell G. Jones. “The liver kinase B1 is a central regulator of T cell development, activation, and metabolism.J Immunol 187, no. 8 (October 15, 2011): 4187–98. https://doi.org/10.4049/jimmunol.1100367.
MacIver NJ, Blagih J, Saucillo DC, Tonelli L, Griss T, Rathmell JC, et al. The liver kinase B1 is a central regulator of T cell development, activation, and metabolism. J Immunol. 2011 Oct 15;187(8):4187–98.
MacIver, Nancie J., et al. “The liver kinase B1 is a central regulator of T cell development, activation, and metabolism.J Immunol, vol. 187, no. 8, Oct. 2011, pp. 4187–98. Pubmed, doi:10.4049/jimmunol.1100367.
MacIver NJ, Blagih J, Saucillo DC, Tonelli L, Griss T, Rathmell JC, Jones RG. The liver kinase B1 is a central regulator of T cell development, activation, and metabolism. J Immunol. 2011 Oct 15;187(8):4187–4198.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

October 15, 2011

Volume

187

Issue

8

Start / End Page

4187 / 4198

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Protein Serine-Threonine Kinases
  • Mice, Knockout
  • Mice
  • Lymphocyte Activation
  • Immunology
  • Immunoblotting
  • Homeostasis