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Y. Chen, S. K. Chauhan, A. Okanobo, D. R. Saban, R. Dana; Regulatory Effects of Early NK Cell Responses on Adaptive Immunity in Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4313.
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© ARVO (1962-2015); The Authors (2016-present)
CD4+ T cells producing IFN-γ and IL-17 are critical for generation of ocular surface inflammation in dry eye disease (DED). The aim of this study was to determine whether these adaptive responses are regulated by natural killer (NK) cells.
The kinetics of NK cells from ocular surface and regional draining lymph nodes in DED were analyzed by real-time PCR and flow cytometry at different time points. Mice in which NK cells were depleted (by anti-asialo GM1 antibody treatment) were assessed for development of DED. The mRNA expression levels of IFN-γ and IL-17 in ocular surface and draining lymph nodes from both NK cell-depleted and control DED mice were measured by real-time PCR. Moreover, draining lymph nodes were further evaluated for T cell-related cytokines as well as maturational status of antigen-presenting cells (APC).
Significant increases of NK1.1 mRNA in the conjunctiva and of the frequency of IFN-γ-secreting NK cells in regional draining lymph nodes were observed during the very early disease phase. Upon NK cell depletion, mice under DED induction showed a markedly decreased disease severity, which correlated with early diminished IFN-γ but enhanced IL-17 production in both the conjunctiva and draining lymph nodes. Furthermore, maturation of APC in draining lymph nodes was delayed by NK cell depletion, along with a substantially decreased expression level of IL-12 mRNA, but increased expression levels of IL-6 and IL-23 in the early disease induction phase. There was no significant change in Foxp3 mRNA transcripts levels.
These findings suggest a disease-promoting role of NK cells in the development of DED, an effect that is possibly mediated by cross-regulating the generation of different components of autoreactive CD4+ T cells in the disease initiation phase.
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