| First Author | Rodenberg RR | Year | 2024 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 65 |
| Issue | 13 | Pages | 16 |
| PubMed ID | 39504049 | Mgi Jnum | J:358450 |
| Mgi Id | MGI:7780840 | Doi | 10.1167/iovs.65.13.16 |
| Citation | Rodenberg RR, et al. (2024) gammadelta T17 Cells Regulate the Acute Antiviral Response of NK Cells in HSV-1-Infected Corneas. Invest Ophthalmol Vis Sci 65(13):16 |
| abstractText | PURPOSE: To determine whether gammadelta T cells regulate natural killer (NK) cells in the herpes simplex virus 1 (HSV-1)-infected cornea. METHODS: CD57Bl/6 (wild-type [WT]), TCRdelta-/-, and IFN-gamma-/- mice were infected intracorneally with HSV-1. TCR-/- mice were treated with IL-17A at 24 hours post-infection (PI), and the WT mice received treatments of fingolimod (FTY720) and anti-IL-17A. At 48 hours PI, corneas were excised, and intracellular staining flow cytometry was performed, as well as multiplex analysis. Additionally, single-cell RNA sequencing (scRNAseq) was done to analyze the transcriptome of NK cells from WT and TCRdelta-/- mice. RESULTS: In mice lacking gammadelta T cells, there were significantly fewer NK cells following ocular HSV-1 infection. This reduction of NK cells corresponded with lower levels of cytokines and chemokines associated with the antiviral response. Furthermore, NK cells from WT mice had enriched IL-17A signaling compared to those from TCRdelta-/- mice. The NK cell response was partially rescued in TCRdelta-/- mice by administration of IL-17A. Correspondingly, the NK cell response could be blunted in WT mice by administration of anti-IL-17A. Finally, IFN-gamma-/- mice had significantly less IL-17A production compared to WT mice. CONCLUSIONS: gammadelta T17 cells promote NK cell accumulation in HSV-1-infected corneas. In turn, NK cells secrete IFN-gamma, which negatively regulates further IL-17A production by gammadelta T cells. |
