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

作者：Reynolds Joseph M; Martinez Gustavo J; Chung Yeonseok; Dong Chen^*

来源：Proceedings of the National Academy of Sciences, 2012, 109(32): 13064-13069.

DOI：10.1073/pnas.1120585109

• innate T cell activation
• multiple sclerosis

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(-/-) gamma delta T cells were defective in IL-17 and IFN-gamma 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.

• 出版日期2012-8-7