A mutation within the SH2 domain of slp‐76 regulates the tissue distribution and cytokine production of iNKT cells in mice
A mutation within the SH2 domain of slp‐76 regulates the tissue distribution and cytokine production of iNKT cells in mice
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slpâ76 SH2 结构域内的突变调节小鼠 iNKT 细胞的组织分布和细胞因子产生
DOI：
10.1002/eji.201646331
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发表时间：
2016
影响因子：
5.4
通讯作者：
Mattner J
中科院分区：
文献类型：
--
作者：
Danzer C;Koller A;Baier J;Arnold H;Giessler C;Opoka R;Schmidt S;Willers M;Mihai S;Parsch H;Wirtz S;Daniel C;Reinhold A;Engelmann S;Kliche S;Bogdan C;Hoebe K;Mattner J
TCR结扎对T淋巴细胞的选择、激活和整合素表达至关重要。在这里，我们探讨了TCR接头蛋白slp - 76在iNKT细胞生物学中的作用。与B6对照相比，slp‐76ace/acemice在slp‐76的SH2‐结构域中携带错义突变（Thr428Ile），胸腺和淋巴结的iNKT细胞增加，但脾脏和肝脏的iNKT细胞减少，同时ADAP表达和细胞因子反应减少。在ADAP缺陷小鼠的肝脏和脾脏中观察到iNKT细胞的类似减少。与ADAP−/−iNKT细胞一样，slp‐76ace/aceiNKT细胞的特征是CD11b表达增强，与TCR即时早期基因enur77的诱导受损和对ICAM‐1的粘附降低相关。此外，CD11b -内在效应抑制细胞因子释放、大豆蛋白A介导的炎症和iNKT -细胞在肝脏中的积累。与B6和ADAP−/−小鼠不同，转录因子Id3和PLZF的表达降低，而NP‐1‐的表达在slp‐76ace/acemice中增强。阻断NP‐1可降低外周血淋巴结中iNKT细胞的恢复，这表明NP‐1是iNKT细胞特异性粘附因子。因此，slp - 76通过ADAP依赖性和非依赖性机制参与调节iNKT细胞的组织分布、PLZF和细胞因子表达。
TCR ligation is critical for the selection, activation, and integrin expression of T lymphocytes. Here, we explored the role of the TCR adaptor protein slp‐76 on iNKT‐cell biology. Compared to B6 controls,slp‐76ace/acemice carrying a missense mutation (Thr428Ile) within the SH2‐domain of slp‐76 showed an increase in iNKT cells in the thymus and lymph nodes, but a decrease in iNKT cells in spleens and livers, along with reduced ADAP expression and cytokine response. A comparable reduction in iNKT cells was observed in the livers and spleens of ADAP‐deficient mice. Like ADAP−/−iNKT cells,slp‐76ace/aceiNKT cells were characterized by enhanced CD11b expression, correlating with an impaired induction of the TCR immediate‐early geneNur77and a decreased adhesion to ICAM‐1. Furthermore, CD11b‐intrinsic effects inhibited cytokine release, concanavalin A‐mediated inflammation, and iNKT‐cell accumulation in the liver. Unlike B6 and ADAP−/−mice, the expression of the transcription factors Id3 and PLZF was reduced, whereas NP‐1‐expression was enhanced inslp‐76ace/acemice. Blockade of NP‐1 decreased the recovery of iNKT cells from peripheral lymph nodes, identifying NP‐1 as an iNKT‐cell‐specific adhesion factor. Thus, slp‐76 contributes to the regulation of the tissue distribution, PLZF, and cytokine expression of iNKT cells via ADAP‐dependent and ‐independent mechanisms.
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影响因子：
2.8
作者：
Wang, Xiaobo;Lu, Xiong;Hu, Tao;Xue, Shuang;Xu, Wenjian;Tang, Wanjie
通讯作者：
Tang, Wanjie
转录因子 PLZF 指导 NKT 细胞谱系的效应程序。
影响因子：
32.4
作者：
Savage, Adam K.;Constantinides, Michael G.;Han, Jin;Picard, Damien;Martin, Emmanuel;Li, Bofeng;Lantz, Olivier;Bendelac, Albert
通讯作者：
Bendelac, Albert
影响因子：
4.4
作者：
M. Emoto;H. Mittrücker;Rudolf Schmits;Tak W. Mak;Stefan H. E. Kaufmann
通讯作者：
M. Emoto;H. Mittrücker;Rudolf Schmits;Tak W. Mak;Stefan H. E. Kaufmann
DOI：
10.1073/pnas.94.14.7493
发表时间：
1997-07-08
影响因子：
11.1
作者：
DaSilva, AJ;Li, ZW;Rudd, CE
通讯作者：
Rudd, CE
Grb2 接头蛋白、Sos 交换因子和 36 kDa 膜结合酪氨酸磷蛋白的复合物参与 T 细胞中 ras 的激活。
DOI：
10.1016/s0021-9258(17)37070-9
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
L. Buday;S. Egan;P. R. Viciana;D. Cantrell;J. Downward
通讯作者：
J. Downward