| First Author | Varanasi SK | Year | 2018 |
| Journal | Mucosal Immunol | Volume | 11 |
| Issue | 6 | Pages | 1705-1715 |
| PubMed ID | 30087443 | Mgi Jnum | J:319319 |
| Mgi Id | MGI:6863680 | Doi | 10.1038/s41385-018-0058-8 |
| Citation | Varanasi SK, et al. (2018) Role of IL-18 induced Amphiregulin expression on virus induced ocular lesions. Mucosal Immunol 11(6):1705-1715 |
| abstractText | This report deals with the possible mechanism by which IL-18 can contribute to the control and resolution of inflammatory lesions in the cornea caused by herpes simplex virus infection. Our results demonstrate that the expression of the IL-18R by both regulatory T cells (Treg) and effector T cells was a pivotal event that influenced lesion pathogenesis. The engagement of IL-18R on Treg with its cytokine ligand resulted in Amphiregulin expression a molecule associated with tissue repair. In support of this scheme of events, lesion severity became more severe in animals unable to express the IL-18R because of gene knockout and was reduced in severity when IL-18 was overexpressed in the cornea. These changes in lesion severity correlated with the frequency and number of both Treg and Teff that expressed Amphiregulin. Additional experiments indicated that IL-12 and IL-18 acted synergistically to enhance Amphiregulin expression in Treg, an event partly dependent on P38 MAPK activity. Finally, sub-conjunctival administration of Amphiregulin resulted in resolution of both developing and developed lesions. Thus, overall our results imply that IL-18 may participate in controlling the severity of SK and contribute to tissue repair by converting both Treg and effector T cells into those that produce Amphiregulin. |
