Schnurri 3 promotes Th2 cytokine production during the late phase of T-cell antigen stimulation.
Schnurri 3 promotes Th2 cytokine production during the late phase of T-cell antigen stimulation.
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在t细胞抗原刺激的后期，Schnurri 3促进Th2细胞因子的产生。
DOI：
10.1002/eji.202149633
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发表时间：
2022-07
影响因子：
5.4
通讯作者：
Iwashima, Makio
中科院分区：
文献类型：
--
作者：
Cunha, Christina;Koike, Toru;Seki, Yoichi;Yamamoto, Mutsumi;Iwashima, Makio
Th 1和Th 2极化由许多因素的协调决定，包括抗原-受体相互作用的亲和力和强度、主要的细胞因子环境和存在的共刺激分子。在这里，我们表明，Schnurri（SHN）蛋白在Th 1和Th 2极化中具有不同的作用。SHN 2以前被发现阻断GATA 3和Th 2分化的诱导。我们发现，与SHN 2相反，SHN 3对IL-4产生和Th 2极化至关重要。刺激强度控制SHN 2和SHN 3表达模式，其中较高剂量的抗原受体刺激促进SHN 3表达和IL-4产生，沿着SHN 2表达的抑制。SHN 3缺陷型T细胞在IL-4产生和AP-1组分表达方面表现出实质性缺陷，特别是c-Jun和Jun B。这种早期IL-4产生的丧失导致GATA 3表达减少和Th 2分化受损。总之，这些发现揭示了SHN 3作为一种新的，关键的调节Th 2的发展。早期的研究表明，抗原受体信号强度可以决定Th 1/Th 2极化。延长的抗原受体信号传导可以诱导转录因子SHN-3的表达，SHN-3是Th 2细胞分化所必需的。SHN-3表达的缺失会导致IL-4产生减少，并导致体内Th 1优势免疫应答。
Th1 and Th2 polarization is determined by the coordination of numerous factors including the affinity and strength of the antigen‐receptor interaction, predominant cytokine environment, and costimulatory molecules present. Here, we show that Schnurri (SHN) proteins have distinct roles in Th1 and Th2 polarization. SHN2 was previously found to block the induction of GATA3 and Th2 differentiation. We found that, in contrast to SHN2, SHN3 is critical for IL‐4 production and Th2 polarization. Strength of stimulation controls SHN2 and SHN3 expression patterns, where higher doses of antigen receptor stimulation promoted SHN3 expression and IL‐4 production, along with repression of SHN2 expression. SHN3‐deficient T cells showed a substantial defect in IL‐4 production and expression of AP‐1 components, particularly c‐Jun and Jun B. This loss of early IL‐4 production led to reduced GATA3 expression and impaired Th2 differentiation. Together, these findings uncover SHN3 as a novel, critical regulator of Th2 development. Earlier studies showed that antigen receptor signal strength can dictate Th1/Th2 polarization. Prolonged antigen receptor signaling induces the expression of a transcription factor, SHN‐3, which is required for initial Th2‐cell differentiation. Loss of SHN‐3 expression causes a reduction in IL‐4 production and causes Th1‐dominant in vivo immune responses.
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DOI：
10.1073/pnas.2133048100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Hong, JW;Allen, CE;Wu, LC
通讯作者：
Wu, LC
影响因子：
56.9
作者：
FRASER, JD;IRVING, BA;WEISS, A
通讯作者：
WEISS, A
影响因子：
32.4
作者：
Esensten JH;Helou YA;Chopra G;Weiss A;Bluestone JA
通讯作者：
Bluestone JA
影响因子：
15.3
作者：
Kimura, MY;Hosokawa, H;Yamashita, M;Hasegawa, A;Iwamura, C;Watarai, H;Taniguchi, M;Takagi, T;Ishii, S;Nakayama, T
通讯作者：
Nakayama, T
影响因子：
56.9
作者：
Finotto, S;Neurath, MF;Glimcher, LH
通讯作者：
Glimcher, LH