TLR2 Involved in Naive CD4+ T Cells Rescues Stress-Induced Immune Suppression by Regulating Th1/Th2 and Th17

Neuroimmunomodulation. 2015;22(5):328-36. doi: 10.1159/000371468. Epub 2015 Feb 25.

Abstract

Stress, either physical or psychological, can have a dramatic impact on our immune system. There has been little progress, however, in understanding chronic stress-induced immunosuppression. Naive CD4+ T cells could modulate immune responses via differentiation to T helper (Th) cells. In this study, we showed that stress promotes the release of the Th1 cytokines interferon (IFN)-γ and tumor necrosis factor (TNF)-α, the Th2 cytokines interleukin (IL)-4 and IL-10 and the Th17 cytokine IL-17 of splenic naive CD4+ T cells. This suggests that stress promotes the differentiation of naive CD4+ T cells to Th1, Th2 and Th17 cells. Knockout strategies verified that TLR2 might modulate the differentiation of Th1/Th2 cells by inhibiting p38 mitogen-activated protein kinase (MAPK). Taken together, our data suggest that chronic stress induces immune suppression by targeting TLR2 and p38 MAPK in naive CD4+ T cells.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Cytokines / metabolism
  • Imidazoles / pharmacology
  • Immunosuppression Therapy*
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pyridines / pharmacology
  • Stress, Psychological / immunology*
  • Stress, Psychological / pathology*
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Th2 Cells / immunology
  • Time Factors
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*
  • Up-Regulation

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Imidazoles
  • Pyridines
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • SB 203580