Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation

Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):13064-9. doi: 10.1073/pnas.1120585109. Epub 2012 Jul 23.


Toll-like receptors (TLRs) are critical components of innate immunity and function as rapid pathogen sensors. TLR4 is expressed on CD4(+) T cells as well, the functional significance of which is unclear. In this study, we analyzed the function of TLR4 in T cells but did not find a role in promoting T helper (Th) cell polarization. Instead, TLR4 ligation enhanced both CD4(+) T-cell proliferation and survival in vitro. Using the experimental autoimmune encephalomyelitis (EAE) model, we found that the loss of TLR4 solely in CD4(+) T cells almost completely abrogated disease symptoms, mainly through blunted Th17 and, to a lesser degree, Th1 responses. Moreover, Tlr4(-/-) γδ T cells were defective in IL-17 and IFN-γ production following EAE induction. This study supports an important role of this innate receptor in the direct regulation of T-cell activation and survival during autoimmune inflammation.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Hemocyanins / immunology
  • Homeodomain Proteins / genetics
  • Immunity, Innate / immunology*
  • Interferon-gamma / immunology
  • Interleukin-17 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Real-Time Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Signal Transduction / immunology*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology*
  • Toll-Like Receptor 4 / metabolism


  • Homeodomain Proteins
  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • RAG-1 protein
  • Interferon-gamma
  • Hemocyanins
  • keyhole-limpet hemocyanin