期刊
CELL REPORTS
卷 32, 期 3, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.107911
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资金
- Japan Society for the Promotion of Science [22790480, 24229004]
- Grants-in-Aid for Scientific Research [22790480] Funding Source: KAKEN
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 kappa B (NF-kappa B) and ERK, leading to much higher production of interferon-gamma (IFN-gamma) 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-gamma 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-gamma production by effector T cells.
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