Proatherogenic conditions promote autoimmune T helper 17 cell responses in vivo

Immunity. 2014 Jan 16;40(1):153-65. doi: 10.1016/j.immuni.2013.11.021. Epub 2014 Jan 9.


Patients with systemic autoimmune diseases show increased incidence of atherosclerosis. However, the contribution of proatherogenic factors to autoimmunity remains unclear. We found that atherogenic mice (herein referred to as LDb mice) exhibited increased serum interleukin-17, which was associated with increased numbers of T helper 17 (Th17) cells in secondary lymphoid organs. The environment within LDb mice was substantially favorable for Th17 cell polarization of autoreactive T cells during homeostatic proliferation, which was considerably inhibited by antibodies directed against oxidized low-density lipoprotein (oxLDL). Moreover, the uptake of oxLDL induced dendritic-cell-mediated Th17 cell polarization by triggering IL-6 production in a process dependent on TLR4, CD36, and MyD88. Furthermore, self-reactive CD4(+) T cells that expanded in the presence of oxLDL induced more profound experimental autoimmune encephalomyelitis. These findings demonstrate that proatherogenic factors promote the polarization and inflammatory function of autoimmune Th17 cells, which could be critical for the pathogenesis of atherosclerosis and other related autoimmune diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Blocking / metabolism
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology*
  • Autoimmunity
  • CD36 Antigens / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Interleukin-17 / metabolism*
  • Interleukin-6 / metabolism
  • Lipoproteins, LDL / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / metabolism
  • Th17 Cells / immunology*
  • Toll-Like Receptor 4 / metabolism


  • Antibodies, Blocking
  • CD36 Antigens
  • Interleukin-17
  • Interleukin-6
  • Lipoproteins, LDL
  • Myeloid Differentiation Factor 88
  • Toll-Like Receptor 4
  • oxidized low density lipoprotein