Wiskott-Aldrich syndrome protein is required for homeostasis and function of invariant NKT cells.
Wiskott-Aldrich syndrome protein is required for homeostasis and function of invariant NKT cells.
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DOI：
10.4049/jimmunol.0804256
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发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Rawlings DJ
中科院分区：
文献类型：
--
作者：
Astrakhan A;Ochs HD;Rawlings DJ
NKT细胞包含表达半不变T细胞受体的单独T谱系。典型的iNKT细胞特异性识别由CD 1d（一种MHC I类分子）呈递的脂质抗原。iNKT细胞部分地作为细菌感染的初始应答者发挥作用，并在免疫监视和肿瘤排斥中发挥作用。Wiskott-Aldrich综合征蛋白（WASp）是细胞刺激和细胞骨架重排之间的关键联系。虽然我们和其他人已经确定了WASp在T调节细胞和边缘区B细胞的稳态中的关键作用，但关于WASp在iNKT谱系中的作用的数据很少。对杂合子雌性WASp小鼠中表达WASp的细胞群的分析显示，WASp+与WASp− iNKT细胞相比具有显著的选择优势。虽然成年WASp缺陷（WASp−/−）小鼠的胸腺和BM iNKT数量正常，但我们观察到脾脏和肝脏中iNKT细胞数量减少2-3倍。这种外周iNKT缺陷部分是由于iNKT稳态缺陷而表现出来的。在竞争性再增殖模型中，WASp−/− iNKT细胞表现出整合素表面表达水平降低以及外周组织内归巢和/或滞留减少。此外，对年轻小鼠的分析表明，WASp对胸腺iNKT细胞的成熟和排出都很重要。WASp−/− iNKT细胞也表现出抗原诱导的增殖和细胞因子产生的显著减少。我们的研究结果强调了WASp在iNKT发育、稳态和激活中的关键作用，并将iNKT功能障碍确定为可能导致WAS患者临床特征的额外因素。
NKT cells comprise a separate T lineage expressing semi-invariant T cell receptors. Canonical iNKT cells specifically recognize lipid antigens presented by CD1d, a MHC Class I-like molecule. iNKT cells function, in part, as initial responders to bacterial infection and play a role in immune surveillance and tumor rejection. The Wiskott-Aldrich Syndrome protein (WASp) serves as a crucial link between cellular stimuli and cytoskeletal rearrangements. While we and others have identified a key role for WASp in homeostasis of T-regulatory and marginal zone B cells, little data exist regarding the role for WASp within the iNKT lineage. Analysis of WASp-expressing cell populations in heterozygous female WASp mice revealed a substantial selective advantage for WASp+ vs. WASp− iNKT cells. While adult WASp-deficient (WASp−/−) mice had normal thymic and BM iNKT numbers, we observed 2–3 fold reduction in the numbers of iNKT cells in the spleen and liver. This peripheral iNKT deficit is manifested, in part, due to defective iNKT homeostasis. WASp−/− iNKT cells exhibited reduced levels of integrin surface expression and decreased homing and/or retention within peripheral tissues in a competitive repopulation model. In addition, analysis of young mice showed that WASp is important for both maturation and egress of thymic iNKT cells. WASp−/− iNKT cells also exhibited a marked reduction in antigen-induced proliferation and cytokine production. Our findings highlight the crucial role for WASp in iNKT development, homeostasis and activation, and identify iNKT dysfunction as an additional factor likely to contribute to the clinical features observed in WAS patients.
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DOI：
10.1084/jem.192.5.741
发表时间：
2000-09-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Matsuda JL;Naidenko OV;Gapin L;Nakayama T;Taniguchi M;Wang CR;Koezuka Y;Kronenberg M
通讯作者：
Kronenberg M
DOI：
10.1084/jem.20030976
发表时间：
2004-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Badour K;Zhang J;Shi F;Leng Y;Collins M;Siminovitch KA
通讯作者：
Siminovitch KA
影响因子：
4.4
作者：
Carlyle, James R.;Mesci, Aruz;Makrigiannis, Andrew P.
通讯作者：
Makrigiannis, Andrew P.
影响因子：
4.8
作者：
Allende, Maria L.;Zhou, Dapeng;Proia, Richard L.
通讯作者：
Proia, Richard L.
影响因子：
4.4
作者：
Akbari, Omid;Stock, Philippe;DeKruyff, Rosemarie H.
通讯作者：
DeKruyff, Rosemarie H.