| First Author | Hu MD | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 2 | Pages | 747-756 |
| PubMed ID | 29884699 | Mgi Jnum | J:264061 |
| Mgi Id | MGI:6192228 | Doi | 10.4049/jimmunol.1701603 |
| Citation | Hu MD, et al. (2018) Epithelial IL-15 Is a Critical Regulator of gammadelta Intraepithelial Lymphocyte Motility within the Intestinal Mucosa. J Immunol 201(2):747-756 |
| abstractText | Intraepithelial lymphocytes (IELs) expressing the gammadelta TCR (gammadelta IELs) provide continuous surveillance of the intestinal epithelium. However, the mechanisms regulating the basal motility of these cells within the epithelial compartment have not been well defined. We investigated whether IL-15 contributes to gammadelta IEL localization and migratory behavior in addition to its role in IEL differentiation and survival. Using advanced live cell imaging techniques in mice, we find that compartmentalized overexpression of IL-15 in the lamina propria shifts the distribution of gammadelta T cells from the epithelial compartment to the lamina propria. This mislocalization could be rescued by epithelial IL-15 overexpression, indicating that epithelial IL-15 is essential for gammadelta IEL migration into the epithelium. Furthermore, in vitro analyses demonstrated that exogenous IL-15 stimulates gammadelta IEL migration into cultured epithelial monolayers, and inhibition of IL-2Rbeta significantly attenuates the basal motility of these cells. Intravital microscopy showed that impaired IL-2Rbeta signaling induced gammadelta IEL idling within the lateral intercellular space, which resulted in increased early pathogen invasion. Similarly, the redistribution of gammadelta T cells to the lamina propria due to local IL-15 overproduction also enhanced bacterial translocation. These findings thus reveal a novel role for IL-15 in mediating gammadelta T cell localization within the intestinal mucosa and regulating gammadelta IEL motility and patrolling behavior as a critical component of host defense. |
