| First Author | Wang X | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 12 | Pages | 2351-9 |
| PubMed ID | 25348153 | Mgi Jnum | J:219661 |
| Mgi Id | MGI:5629467 | Doi | 10.1084/jem.20140646 |
| Citation | Wang X, et al. (2014) GPR18 is required for a normal CD8alphaalpha intestinal intraepithelial lymphocyte compartment. J Exp Med 211(12):2351-9 |
| abstractText | Intraepithelial lymphocytes (IELs) play an important role in maintaining the physiology of the small intestine. The majority of mouse IELs express CD8alphaalpha and are either gammadelta or alphabeta T cells. Although the development and homing of CD8alphaalpha 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 CD8alphaalpha IELs and that mice lacking this orphan receptor have reduced numbers of gammadeltaT IELs. Mixed bone marrow chimera experiments reveal a markedly reduced contribution of GPR18-deficient cells to the CD8alphaalpha IEL compartment and a reduction in the CD8alphabeta T cell subset. These defects could be rescued by transduction with a GPR18-expressing retrovirus. The GPR18-deficient gammadeltaT IELs that remained in mixed chimeras had elevated Thy1, and there were less granzyme B(+) and Vgamma7(+) cells, indicating a greater reduction in effector-type cells. Flow cytometric analysis indicated GPR18 deficiency more strongly affected the CD8alphaalpha cells in the intraepithelial compared with the adjacent lamina propria compartment. These findings establish a requirement for GPR18 in CD8alphaalpha and CD8alphabeta IELs, and we suggest the receptor has a role in augmenting the accumulation of CD8 T cells in the intraepithelial versus lamina propria compartment. |
