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C. Tan, G. Shi, B. P. Vistica, E. F. Wawrousek, I. Gery; Expression Profiles of Apoptosis-Related and Co-Inhibitory Molecules by Eyes Developing Th1- or Th17-Induced Inflammation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5548.
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Apoptosis and co-inhibition are major regulatory components of immunopathogenic processes. Apoptosis is initiated by two mechanisms, the intrinsic and extrinsic pathways, with different molecules taking part in each of these pathways. Co-inhibition, a biological activity related to co-stimulation, is mediated mainly by program death-1 (PD-1) and its ligands, PD-L1 and PD-L2. This study was aimed at investigating the involvement of several molecules of each family in the inflammatory processes induced in mouse eyes expressing hen egg lysozyme (HEL) by adoptively transferred polarized Th1 or Th17 cells specific against HEL (Cox et al, J. Immunol. 180:7414, 2008).
Total RNA extracted from mouse eyes with inflammation induced by Th1 or Th17, as well as naïve control eyes, was used for first-strand cDNA synthesis. Transcript levels of tested molecules were determined by real-time PCR.
The inflammatory processes had little effects on the expression levels of intrinsic pathway molecules Bad and Bax, as well as Bcl-2; similar transcript levels were seen in inflamed eyes and their naïve control. In contrast, transcript levels of extrinsic pathway molecules Fas, Fas-L and TRAIL were strikingly higher in inflamed eyes than in naïve control eyes. Interestingly, whereas Fas transcript expression was similar in Th1 and Th17 recipient eyes, expression of Fas-L and, in particular, of TRAIL was higher in Th1 than in Th17 recipient eyes. The transcript levels of PD-1 and PD-Ls were also significantly higher in mouse eyes with inflammation than in naïve control eyes and, remarkably, PD-1 and PD-L2 transcripts expression were also higher in Th1 than in Th17 recipient eyes.
Apoptotic processes in mouse eyes developing immune-mediated inflammation are initiated and driven by extrinsic pathway molecules, not by intrinsic pathway molecules. The higher expression of apoptosis-related and co-inhibitory molecules in Th1 recipient eyes indicates that Th1 cells are more susceptible to apoptosis than Th17 cells.
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