Abstract
Purpose :
Fungal keratitis (FK) is a serious and destructive eye disease, characterized by ulcers. Understanding the mechanism of adaptive immunity in corneal infection is important in the treatment and prevention of FK. Our previous studies reported innate immunity and adaptive immunity in human corneal epithelial cells (HCECs). The present study demonstrated the potential role of thymic stromal lymphopoietin (TSLP), and that IL-4 promotes expression of TSLP in an inflammation loop in adaptive immunity of FK.
Methods :
Mice were evenly divided into control, PBS, Aspergillus fumigatus (AF), scramble siRNA, TSLP siRNA, rTSLP, IgG, rIFN-γ, rIL-4, rIL-13, rIL-17A, and rIL-17F groups. Aspergillus fumigatus hyphae -induced fungal keratitis models were successfully established. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to determine the mRNA and protein levels of TSLP, cell cytokines, such as interferon (IFN)-γ, interleukin (IL)-4, IL-13, IL-17A, IL-17F, and TGF-β, and transcription factors, such as T-bet, GATA-3, STAT-3, and FoxP3 in the cornea. Immunofluorescent staining was used to observed the location of cytokines after A. fumigatus hyphae infection.
Results :
Compared with the control group, expressions of TSLP, IFN-γ, T-bet, GATA-3, and STAT-3 were high at 24h, and IL-4, IL-13, IL-17A, and IL-17F were increased at 5d in the AF group. TGF-β and FoxP3 were not changed compared with the control group. IL-4, IL-13, and GATA-3 decreased in the TSLP siRNA group and increased in the rTSLP group compared with the AF group. TSLP increased in the rIL-4 group and there was no significant change in rIFN-γ, rIL-13, rIL-17A, and rIL-17F groups.
Conclusions :
The study showed that TSLP induced the Th2 immune response and promoted T cell differentiation in the direction of Th2 in vivo after establishment of fungal keratitis. IL-4 could promote the secretion of TSLP in an inflammation loop.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.