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Yun Zhang, Xin Chen, Ruzhi Deng, Wei Chi, Stephen C Pflugfelder, De-Quan Li; IL-27 Signaling Deficiency Develops Th17-enhanced Allergic Inflammation. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6722.
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While most studies focus on pro-allergic cytokines, the protective role of immunosuppressive cytokines in allergic inflammation is not well elucidated. This study was to explore a novel anti-inflammatory role and molecular mechanism of IL-27 in pathogenesis of allergic inflammation.
A murine model of experimental allergic conjunctivitis (EAC) was induced in wild-type C57BL/6 or IL-27Rα deficient (WSX-1-/-) mice by short ragweed pollen, with untreated or PBS-treated mice as controls. The serum, eyeballs, conjunctiva, cervical lymph nodes (CLNs) were used for study. Gene expression was determined by RT-qPCR, immunostaining. ELISA and Western blotting evaluated protein production and activation.
Typical allergic manifestations and stimulated TSLP signaling and Th2 responses were observed in ocular surface of EAC models in C57BL/6 mice. The decrease of IL-27 at mRNA (IL-27/EBI3) and protein levels were detected in serum, conjunctiva and CLN, as evaluated by RT-qPCR, immunofluorescent staining, ELISA and Western blotting. EAC induced in WSX-1-/- mice showed aggravated allergic signs with higher TSLP-driven Th2-dominant inflammation, accompanied by stimulated Th17 responses, including IL-17A, IL-17F, and transcription factor RORγt. In contrast, Th1 cytokine IFNγ and Treg marker IL-10, with their respective transcription factors T-bet and foxp3 were largely suppressed. Interestingly, imbalanced activation between reduced phosphor (P)-STAT1 and stimulated P-STAT6 were revealed in EAC, especially WSX-1-/--EAC mice.
These findings demonstrate that IL-27 plays an importantly protective role in allergic disease by suppressing Th2 and Th17 hyper-responses, and IL-27 signaling deficiency develops a Th17-enhanced Th2-dominant Allergic Inflammation. The findings provide a new insight on allergic pathogenesis and the therapeutic potential to treat allergic diseases.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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