Abstract
Purpose: :
The recently discovered population of Th17 cells has been shown to play a major role in immune-mediated inflammation, including EAU. We previously showed that transgenic (Tg) mice expressing IL-1 or IL-7 under control of the aA-crystallin promoter develop severe ocular inflammation. This study was aimed at investigating the involvement of Th17 and Th1 in the pathogenic process in eyes of these Tg mice.
Methods: :
Total RNA was extracted from eyes of the Tg mice after perfusion with PBS to remove blood from the eyes. Extracted total RNA was used for first-strand cDNA synthesis and real-time PCR was used to quantify expression levels of the selected genes.
Results: :
Eyes of IL-1 Tg mice were found to express high transcript levels of IL-17, the signature cytokine of Th17, and much lower levels of IFN-γ transcript, the signature cytokine of Th1 cells. In contrast, eyes of IL-7 Tg mice expressed IFN-γ transcript, but no detectable levels of IL-17 transcript. Furthermore, the transcript for ROR-γt, a transcription factor for IL-17, was found in high levels in eyes of IL-1 Tg mice but could not be detected in IL-7 Tg eyes, whereas T-bet, a transcription factor for IFN-γ was found at high levels in IL-7 Tg eyes but only at marginal levels in IL-1 Tg eyes. In addition, Eomes, another transcription factor specific to IFN-γ, was found only in IL-7 Tg mouse eyes. Differences between IL-1 Tg and IL-7 Tg mouse eyes were also noted in their expression of cytokines known to facilitate the production of IFN-γ or IL-17: IL-12p35 transcript levels were higher in IL-7 Tg eyes, whereas the transcript levels of IL-6, IL-23 and TGF-β were remarkably higher in IL-1 Tg eyes.
Conclusions: :
Eyes of IL-1 and IL-7 Tg mice differ profoundly in their expression of signature cytokines and transcription factors specific to Th cell populations, with IL-1 Tg eyes preferentially expressing Th17-specific molecules and IL-7 Tg eyes expressing only Th1-specific molecules.
Keywords: autoimmune disease • inflammation • cytokines/chemokines