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C. Tan, G. Shi, B. P. Vistica, E. F. Wawrousek, I. Gery; Selective Polarization Toward Th17 or Th1 Phenotypes in Mouse Eyes With Inflammation Due to Local Expression of IL-1 or IL-7. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2529. doi: https://doi.org/.
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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.
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.
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.
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.
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