mTORC1 Signaling Controls TLR2-Mediated T-Cell Activation by Inducing TIRAP Expression.

Abstract:

:Effector, but not naïve, 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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Imanishi T,Unno M,Kobayashi W,Yoneda N,Akira S,Saito T

doi

10.1016/j.celrep.2020.107911

subject

Has Abstract

pub_date

2020-07-21 00:00:00

pages

107911

issue

3

issn

2211-1247

pii

S2211-1247(20)30892-5

journal_volume

32

pub_type

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