SLAP deficiency enhances number and function of regulatory T cells preventing chronic autoimmune arthritis in SKG mice.
SLAP deficiency enhances number and function of regulatory T cells preventing chronic autoimmune arthritis in SKG mice.
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DOI：
10.4049/jimmunol.1003601
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发表时间：
2011-02-15
期刊：
影响因子：
--
通讯作者：
Dragone LL
中科院分区：
文献类型：
--
作者：
Peterson LK;Shaw LA;Joetham A;Sakaguchi S;Gelfand EW;Dragone LL
To test if manipulating TCR complex-mediated signaling (TCR signaling) could treat autoimmune disease, we generated the double SKG Src-like adapter protein (SLAP) knockout (DSSKO) mouse model. The SKG mutation in ZAP70 and SLAP have opposing functions on the regulation of TCR signaling. The combination of these two mutations alters TCR signaling in the context of a defined genetic background, uniform environmental conditions, and a well-characterized signaling disruption. In contrast to SKG mice, DSSKO mice do not develop zymosan-induced chronic autoimmune arthritis. This arthritis prevention is not due to significant alterations in thymocyte development or repertoire selection but instead enhanced numbers of regulatory T cells (Tregs) and decreased numbers of Th17 cells skewing the ratio of Tregs to autoreactive effector T cells. Treg depletion and/or functional blockade led to the development of arthritis in DSSKO mice. In vitro suppression of effector T cell proliferation was also enhanced, demonstrating that DSSKO mice have increased numbers of Tregs with increased function. Understanding how TCR signals influence development, expansion, and function of Tregs in DSSKO mice could advance our ability to manipulate Treg biology to treat ultimately autoimmune disease.
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影响因子：
3.7
作者：
Duarte J;Agua-Doce A;Oliveira VG;Fonseca JE;Graca L
通讯作者：
Graca L
ZAP-70 的亚等位基因揭示了自身免疫性疾病与自身免疫反应性的不同胸腺阈值。
DOI：
10.1084/jem.20082902
发表时间：
2009-10-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hsu LY;Tan YX;Xiao Z;Malissen M;Weiss A
通讯作者：
Weiss A
DOI：
10.1084/jem.20080707
发表时间：
2008-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Zhou X;Jeker LT;Fife BT;Zhu S;Anderson MS;McManus MT;Bluestone JA
通讯作者：
Bluestone JA
影响因子：
4.4
作者：
Tanaka, Satoshi;Maeda, Shinji;Sakaguchi, Shimon
通讯作者：
Sakaguchi, Shimon
影响因子：
64.8
作者：
Sakaguchi, N;Takahashi, T;Sakaguchi, S
通讯作者：
Sakaguchi, S