Olivares-Villagómez Danyvid, Mendez-Fernandez Yanice V, Parekh Vrajesh V, Lalani Saif, Vincent Tiffaney L, Cheroutre Hilde, Van Kaer Luc
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17931-6. doi: 10.1073/pnas.0808242105. Epub 2008 Nov 12.
Intestinal intraepithelial lymphocytes (IEL) bear a partially activated phenotype that permits them to rapidly respond to antigenic insults. However, this phenotype also implies that IEL must be highly controlled to prevent misdirected immune reactions. It has been suggested that IEL are regulated through the interaction of the CD8alpha alpha homodimer with the thymus leukemia (TL) antigen expressed by intestinal epithelial cells. We have generated and characterized mice genetically-deficient in TL expression. Our findings show that TL expression has a critical role in maintaining IEL effector functions. Also, TL deficiency accelerated colitis in a genetic model of inflammatory bowel disease. These findings reveal an important regulatory role of TL in controlling IEL function and intestinal inflammation.
肠道上皮内淋巴细胞(IEL)具有部分活化的表型,这使它们能够迅速对抗抗原性损伤作出反应。然而,这种表型也意味着IEL必须受到高度调控,以防止免疫反应的方向错误。有人提出,IEL是通过CD8αα同型二聚体与肠道上皮细胞表达的胸腺白血病(TL)抗原的相互作用来调节的。我们已经培育出TL表达基因缺陷的小鼠并对其进行了表征。我们的研究结果表明,TL表达在维持IEL效应功能方面具有关键作用。此外,在炎症性肠病的遗传模型中,TL缺陷加速了结肠炎的发展。这些发现揭示了TL在控制IEL功能和肠道炎症方面的重要调节作用。