Wang Xiaoming, Sumida Hayakazu, Cyster Jason G
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143 Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143 Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143
J Exp Med. 2014 Nov 17;211(12):2351-9. doi: 10.1084/jem.20140646. Epub 2014 Oct 27.
Intraepithelial lymphocytes (IELs) play an important role in maintaining the physiology of the small intestine. The majority of mouse IELs express CD8αα and are either γδ or αβ T cells. Although the development and homing of CD8αα IELs have been studied in some detail, the factors controlling their homeostasis and positioning are incompletely understood. Here we demonstrate that G protein-coupled receptor 18 (GPR18) is abundantly expressed in CD8αα IELs and that mice lacking this orphan receptor have reduced numbers of γδT IELs. Mixed bone marrow chimera experiments reveal a markedly reduced contribution of GPR18-deficient cells to the CD8αα IEL compartment and a reduction in the CD8αβ T cell subset. These defects could be rescued by transduction with a GPR18-expressing retrovirus. The GPR18-deficient γδT IELs that remained in mixed chimeras had elevated Thy1, and there were less granzyme B(+) and Vγ7(+) cells, indicating a greater reduction in effector-type cells. Flow cytometric analysis indicated GPR18 deficiency more strongly affected the CD8αα cells in the intraepithelial compared with the adjacent lamina propria compartment. These findings establish a requirement for GPR18 in CD8αα and CD8αβ IELs, and we suggest the receptor has a role in augmenting the accumulation of CD8 T cells in the intraepithelial versus lamina propria compartment.
上皮内淋巴细胞（IELs）在维持小肠生理功能中发挥着重要作用。大多数小鼠IELs表达CD8αα，且为γδ或αβ T细胞。尽管对CD8αα IELs的发育和归巢已进行了一些详细研究，但控制其体内平衡和定位的因素仍未完全了解。在此，我们证明G蛋白偶联受体18（GPR18）在CD8αα IELs中大量表达，且缺乏该孤儿受体的小鼠γδT IELs数量减少。混合骨髓嵌合体实验显示，GPR18缺陷细胞对CD8αα IEL区室的贡献显著降低，CD8αβ T细胞亚群也减少。这些缺陷可通过表达GPR18的逆转录病毒转导来挽救。留在混合嵌合体中的GPR18缺陷γδT IELs的Thy1升高，颗粒酶B(+)和Vγ7(+)细胞减少，表明效应型细胞减少更多。流式细胞术分析表明，与相邻的固有层区室相比，GPR18缺陷对上皮内CD8αα细胞的影响更强。这些发现确定了CD8αα和CD8αβ IELs中GPR18的必要性，我们认为该受体在增加上皮内与固有层区室中CD8 T细胞的积累方面发挥作用。
