Skip to main content
release_alert
Welcome to the new Scholars 3.0! Read about new features and let us know what you think.
cancel

ATP-binding cassette transporter G1 negatively regulates thymocyte and peripheral lymphocyte proliferation.

Publication ,  Journal Article
Armstrong, AJ; Gebre, AK; Parks, JS; Hedrick, CC
Published in: J Immunol
January 1, 2010

Cholesterol is a key component of cell membranes and is essential for cell growth and proliferation. How the accumulation of cellular cholesterol affects lymphocyte development and function is not well understood. We demonstrate that ATP-binding cassette transporter G1 (ABCG1) regulates cholesterol homeostasis in thymocytes and peripheral CD4 T cells. Our work is the first to describe a cell type in Abcg1-deficient mice with such a robust change in cholesterol content and the expression of cholesterol metabolism genes. Abcg1-deficient mice display increased thymocyte cellularity and enhanced proliferation of thymocytes and peripheral T lymphocytes in vivo. The absence of ABCG1 in CD4 T cells results in hyperproliferation in vitro, but only when cells are stimulated through the TCR. We hypothesize that cholesterol accumulation in Abcg1(-/-) T cells alters the plasma membrane structure, resulting in enhanced TCR signaling for proliferation. Supporting this idea, we demonstrate that B6 T cells pretreated with soluble cholesterol have a significant increase in proliferation. Cholesterol accumulation in Abcg1(-/-) CD4 T cells results in enhanced basal phosphorylation levels of ZAP70 and ERK1/2. Furthermore, inhibition of ERK phosphorylation in TCR-stimulated Abcg1(-/-) T cells rescues the hyperproliferative phenotype. We describe a novel mechanism by which cholesterol can alter signaling from the plasma membrane to affect downstream signaling pathways and proliferation. These results implicate ABCG1 as an important negative regulator of lymphocyte proliferation through the maintenance of cellular cholesterol homeostasis.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

January 1, 2010

Volume

184

Issue

1

Start / End Page

173 / 183

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • T-Lymphocyte Subsets
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Mice, Inbred C57BL
  • Mice
  • Lipoproteins
  • Immunology
  • Homeostasis
  • Flow Cytometry
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Armstrong, A. J., Gebre, A. K., Parks, J. S., & Hedrick, C. C. (2010). ATP-binding cassette transporter G1 negatively regulates thymocyte and peripheral lymphocyte proliferation. J Immunol, 184(1), 173–183. https://doi.org/10.4049/jimmunol.0902372
Armstrong, Allison J., Abraham K. Gebre, John S. Parks, and Catherine C. Hedrick. “ATP-binding cassette transporter G1 negatively regulates thymocyte and peripheral lymphocyte proliferation.J Immunol 184, no. 1 (January 1, 2010): 173–83. https://doi.org/10.4049/jimmunol.0902372.
Armstrong AJ, Gebre AK, Parks JS, Hedrick CC. ATP-binding cassette transporter G1 negatively regulates thymocyte and peripheral lymphocyte proliferation. J Immunol. 2010 Jan 1;184(1):173–83.
Armstrong, Allison J., et al. “ATP-binding cassette transporter G1 negatively regulates thymocyte and peripheral lymphocyte proliferation.J Immunol, vol. 184, no. 1, Jan. 2010, pp. 173–83. Pubmed, doi:10.4049/jimmunol.0902372.
Armstrong AJ, Gebre AK, Parks JS, Hedrick CC. ATP-binding cassette transporter G1 negatively regulates thymocyte and peripheral lymphocyte proliferation. J Immunol. 2010 Jan 1;184(1):173–183.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

January 1, 2010

Volume

184

Issue

1

Start / End Page

173 / 183

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • T-Lymphocyte Subsets
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Mice, Inbred C57BL
  • Mice
  • Lipoproteins
  • Immunology
  • Homeostasis
  • Flow Cytometry