[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

Essential role of CD11a in CD8+ T-cell accumulation and activation in adipose tissue

Arterioscler Thromb Vasc Biol. 2014 Jan;34(1):34-43. doi: 10.1161/ATVBAHA.113.302077. Epub 2013 Oct 24.

Abstract

Objective: T cells, particularly CD8(+) T cells, are major participants in obesity-linked adipose tissue (AT) inflammation. We examined the mechanisms of CD8(+) T-cell accumulation and activation in AT and the role of CD11a, a β2 integrin.

Approach and results: CD8(+) T cells in AT of obese mice showed activated phenotypes with increased proliferation and interferon-γ expression. In vitro, CD8(+) T cells from mouse AT displayed increased interferon-γ expression and proliferation to stimulation with interleukin-12 and interleukin-18, which were increased in obese AT. CD11a was upregulated in CD8(+) T cells in obese mice. Ablation of CD11a in obese mice dramatically reduced T-cell accumulation, activation, and proliferation in AT. Adoptive transfer showed that CD8(+) T cells from wild-type mice, but not from CD11a-deficient mice, infiltrated into AT of recipient obese wild-type mice. CD11a deficiency also reduced tumor necrosis factor-α-producing and interleukin-12-producing macrophages in AT and improved insulin resistance.

Conclusions: Combined action of cytokines in obese AT induces proliferative response of CD8(+) T cells locally, which, along with increased infiltration, contributes to CD8(+) T-cell accumulation and activation in AT. CD11a plays a crucial role in AT inflammation by participating in T-cell infiltration and activation.

Keywords: adipose tissue; inflammation; insulin resistance; obesity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / immunology*
  • Adoptive Transfer
  • Animals
  • CD11a Antigen / genetics
  • CD11a Antigen / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Chemotaxis, Leukocyte*
  • Disease Models, Animal
  • Inflammation Mediators / metabolism
  • Insulin Resistance
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-18 / metabolism
  • Lymphocyte Activation*
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Obese
  • Obesity / blood
  • Obesity / genetics
  • Obesity / immunology*
  • Panniculitis / blood
  • Panniculitis / genetics
  • Panniculitis / immunology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism
  • Weight Gain

Substances

  • CD11a Antigen
  • Inflammation Mediators
  • Interleukin-18
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interferon-gamma