Modulation of T Cell Signaling by Post-translational Modifications in Autoimmune Diseases

MATSUI YUKIHIDE, KUWABARA TAKU, KONDO MOTONARI

doi:10.14994/tohoigaku.2020-023

総説招聘講演(第74回東邦医学会総会)

リン酸化等の翻訳後修飾が調節する情報伝達系は,成熟や病原体排除といったT細胞のライフサイクルを制御している.制御の結果,T細胞は排除するべき異物に反応し,他の免疫細胞の機能を調節したり,自身もウイルス感染細胞等を傷害する.T細胞受容体(TCR)からの抗原刺激,CD28などの共刺激分子の刺激およびサイトカイン刺激がT細胞の働きをコントロールする.これらの刺激が協調して免疫応答を正に調節する.自己へのT細胞応答は免疫寛容によって負に制御されている.免疫寛容はT細胞の成熟時から始まりその後継続する.成熟過程でTCRを介した閾値を超えたシグナルは中枢性免疫寛容をもたらす.抗原認識時にCD28経路の刺激が無いと末梢性免疫寛容のアナジーが誘導される.リン酸化シグナルの強度や経路は重要であるが最近,T細胞の情報伝達調節にアセチル化による制御機構が明らかにされた.本稿では情報伝達とT細胞機能を概説する.Other: Signaling systems regulated by post-translational modifications, such as phosphorylation, regulate the life cycle of T cells, including maturation and pathogen exclusion. As a result of this regulation, T cells respond to foreign substances to be eliminated, regulating the function of other immune cells and damaging others, such as virally infected cells. Stimulation by antigens via T-cell receptors (TCR), co-stimulatory molecules such as CD28, and cytokines control the function of T cells. These stimuli work together to positively regulate the immune response. T-cell responses to self-antigen are negatively regulated by immune tolerance. Immune tolerance begins at the time of T-cell maturation and continues thereafter. Signals that exceed the threshold via TCR during the maturation process result in central immune tolerance. The absence of stimulation of the CD28 pathway during antigen recognition induces an anergy of peripheral immune tolerance. Although the intensity and pathway of phosphorylation signals are important, a mechanism for T-cell regulation by acetylation of signaling molecules has recently been identified. In this article, we will review signal transduction and T-cell function.

Modulation of T Cell Signaling by Post-translational Modifications in Autoimmune Diseases

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