1. mTORC1 Signaling Controls TLR2-Mediated T-Cell Activation by Inducing TIRAP Expression
- Author
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Takayuki Imanishi, Shizuo Akira, Midori Unno, Wakana Kobayashi, Natsumi Yoneda, and Takashi Saito
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,TIRAP ,T cell ,T-Lymphocytes ,Stimulation ,Mechanistic Target of Rapamycin Complex 1 ,Lymphocyte Activation ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Interferon-gamma ,0302 clinical medicine ,medicine ,Animals ,Cells, Cultured ,Membrane Glycoproteins ,Chemistry ,Effector ,T-cell receptor ,Signal transducing adaptor protein ,Receptors, Interleukin-1 ,Th1 Cells ,Toll-Like Receptor 2 ,Cell biology ,Up-Regulation ,Mice, Inbred C57BL ,TLR2 ,030104 developmental biology ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-6 ,Interleukin-2 ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Summary Effector, but not naive, T cells are activated by toll-like receptor-2 (TLR2) stimulation, leading to cytokine production and proliferation. We found that the differential response is attributable to the lack of expression of the adaptor protein TIRAP in naive T cells. TIRAP expression is induced upon T-cell receptor (TCR) stimulation and sustained by strong interleukin-2 (IL-2) signals. Expression of TIRAP requires TCR- and IL-2-induced mTORC1 activation. TLR2 stimulation induced the activation of nuclear factor κB (NF-κB) and ERK, leading to much higher production of interferon-γ (IFN-γ) by T helper 1 (Th1) cells cultured in a high concentration of IL-2 than by those cultured in a low concentration of IL-2. In contrast, TLR2 stimulation induces mTORC1 activation through TIRAP, which is essential for TLR2-mediated IFN-γ production. These data demonstrate that the mTORC1 signal confers the response to TLR2 signaling by inducing TIRAP expression and that the TIRAP-mTORC1 axis is critical for TLR2-mediated IFN-γ production by effector T cells.
- Published
- 2020