Given the significance of TSLP and JAK/STAT in the Th17 response induced by
A. fumigatus–stimulated DCs, we decided to further study the role of TSLP and JAK/STAT signaling in
A. fumigatus–infected corneas with FK. To clarify the role of TSLP in
A. fumigatus–infected corneas, we pretreated mice by subconjunctival injection with BSA, rmTSLP, NC siRNA, or TSLP siRNA before infection with
A. fumigatus hyphae. The corneal injury degree was determined by clinical scoring at 1 day after infection. These results suggested that corneal damages, including keratitis, necrosis, and epithelial edema, were enhanced in the group treated with rmTSLP, whereas the injuries were less severe in the TSLP siRNA group at 1 day after infection (
Fig. 8A and B). The qRT-PCR results showed that the TSLP levels in the TSLP siRNA group were knocked down to approximately 75% of the normal level seen in the NC siRNA group (
Fig. 8C). The mRNA and protein levels of Th17 cytokines (IL-17A, IL-17F, and IL-22) were evidently decreased in TSLP siRNA-treated corneas compared with the levels in the NC siRNA-treated corneas. However, by comparison, we observed a significant increase in IL-17A, IL-17F, and IL-22 mRNA and protein levels in the mouse corneas with rmTSLP treatment (
Fig. 8D and E). To investigate the function of JAK/STAT in FK, we subconjunctivally injected the mouse corneas with PBS (control), ruxolitinib, or BBI608 before treatment with
A. fumigatus hyphae for 1 day. The corneas showed a severe cellular infiltration with destruction of the corneal epithelium stroma 1 day after
A. fumigatus infection, whereas the corneal inflammatory response was significantly alleviated in the ruxolitinib or BBI608 injected group (
Fig. 8F). The average clinical scores of the ruxolitinib or BBI608-treated corneas were also lower than those of ordinary infected corneas (
Fig. 8G). Consistently, we observed that the mRNA levels and protein secretions of Th17 cytokines (IL-17A, IL-17F, and IL-22) were evidently reduced in the ruxolitinib or BBI608 injected group (
Fig. 8H and I). Taken together, our results suggest that TSLP promoted the disease progression of
A. fumigatus keratitis. However, inhibition of the JAK/STAT signaling pathway reversed the development of FK.