Butyrophilin-like 1 encodes an enterocyte protein that selectively regulates functional interactions with T lymphocytes

Butyrophilin-like 1 encodes an enterocyte protein that selectively regulates functional interactions with T lymphocytes
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DOI:
10.1073/pnas.1010647108
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发表时间:
2011-03-15
影响因子:
11.1
通讯作者:
Hayday, Adrian C.
Hayday, Adrian C.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bas, Anna;Swamy, Mahima;Hayday, Adrian C.

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虽然上皮细胞对T细胞反应的局部调节越来越被认为是重要的,但很少有介导这种调节的分子被鉴定。Skint 1是最近发现的由胸腺上皮细胞和角质形成细胞表达的免疫球蛋白超基因家族的成员,它指定了小鼠表皮上皮内淋巴细胞(IEL)谱系。研究Skint 1相关分子是否可能在其他隔室中调节IEL,本研究的重点是嗜嗜碱性蛋白样1(Btnl 1),它与Skint 1非常相似,主要限于小肠上皮。Btnl 1蛋白主要是细胞质,但可以诱导表面表达,并且在体内可以在IEL附近检测到Btnl 1。在新开发的培养系统中,Btnl 1的增强的上皮细胞表达减弱了细胞对激活的IEL的反应,如通过抑制IL-6和其他炎症介质所证明的。这些发现提供了对新兴遗传数据的独特视角,即Btnl基因可能包含肠道炎症的新的和重要的局部调节因子。
Although local regulation of T-cell responses by epithelial cells is increasingly viewed as important, few molecules mediating such regulation have been identified. Skint1, a recently identified member of the Ig-supergene family expressed by thymic epithelial cells and keratinocytes, specifies the murine epidermal intraepithelial lymphocyte (IEL) repertoire. Investigating whether Skint1-related molecules might regulate IEL in other compartments, this study focuses on buytrophilin-like 1 (Btnl1), which is conspicuously similar to Skint1 and primarily restricted to small intestinal epithelium. Btnl1 protein is mostly cytoplasmic, but surface expression can be induced, and in vivo Btnl1 can be detected adjacent to the IEL. In a newly developed culture system, enforced epithelial cell expression of Btnl1 attenuated the cells' response to activated IEL, as evidenced by suppression of IL-6 and other inflammatory mediators. These findings offer a unique perspective on emerging genetic data that Btnl genes may comprise novel and important local regulators of gut inflammation.