ATP 结合盒转运蛋白 G1 内在调节不变自然杀伤 T 细胞的发育。
ATP-binding cassette transporter G1 intrinsically regulates invariant NKT cell development.
机构信息
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
出版信息
J Immunol. 2012 Dec 1;189(11):5129-38. doi: 10.4049/jimmunol.1201570. Epub 2012 Oct 24.
Abstract
ATP-binding cassette transporter G1 (ABCG1) plays a role in the intracellular transport of cholesterol. Invariant NKT (iNKT) cells are a subpopulation of T lymphocytes that recognize glycolipid Ags. In this study, we demonstrate that ABCG1 regulates iNKT cell development and functions in a cell-intrinsic manner. Abcg1(-/-) mice displayed reduced frequencies of iNKT cells in thymus and periphery. Thymic iNKT cells deficient in ABCG1 had reduced membrane lipid raft content, and showed impaired proliferation and defective maturation during the early stages of development. Moreover, we found that Abcg1(-/-) mice possess a higher frequency of Vβ7(+) iNKT cells, suggesting alterations in iNKT cell thymic selection. Furthermore, in response to CD3ε/CD28 stimulation, Abcg1(-/-) thymic iNKT cells showed reduced production of IL-4 but increased production of IFN-γ. Our results demonstrate that changes in intracellular cholesterol homeostasis by ABCG1 profoundly impact iNKT cell development and function.
摘要
三磷酸腺苷结合盒转运体 G1（ABCG1）在胆固醇的细胞内转运中发挥作用。不变自然杀伤 T（iNKT）细胞是 T 淋巴细胞的一个亚群，能够识别糖脂抗原。在这项研究中，我们证明 ABCG1 以细胞内固有方式调节 iNKT 细胞的发育和功能。ABCG1(-/-) 小鼠的胸腺和外周血中 iNKT 细胞频率降低。缺乏 ABCG1 的胸腺 iNKT 细胞的膜脂筏含量减少，并且在发育的早期阶段显示出增殖受损和成熟缺陷。此外，我们发现 Abcg1(-/-) 小鼠具有更高频率的 Vβ7(+) iNKT 细胞，提示 iNKT 细胞胸腺选择的改变。此外，在对 CD3ε/CD28 刺激的反应中，ABCG1(-/-) 胸腺 iNKT 细胞产生的 IL-4 减少，但 IFN-γ 的产生增加。我们的结果表明，ABCG1 引起的细胞内胆固醇稳态变化显著影响 iNKT 细胞的发育和功能。
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本文引用的文献
1
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Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19719-24. doi: 10.1073/pnas.1113021108. Epub 2011 Nov 17.
2
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3
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