IL-27 signaling deficiency develops Th17-enhanced Th2-dominant inflammation in murine allergic conjunctivitis model.

ABSTRACT: BACKGROUND: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 cellular/molecular mechanism of IL-27 in allergic inflammation. METHODS:A murine model of experimental allergic conjunctivitis (EAC) was induced in BALB/c, C57BL/6 or IL-27R?-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, and protein production and activation were evaluated by immunostaining, ELISA and Western blotting. RESULTS:Typical allergic manifestations and stimulated thymic stromal lymphopoietin (TSLP) signaling and Th2 responses were observed in ocular surface of EAC models in BALB/c and 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 ROR?t. In contrast, Th1 cytokine IFN? 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. CONCLUSION:These findings demonstrated a natural protective mechanism by IL-27, of which signaling deficiency develops a Th17-type hyperresponse that further aggravates Th2-dominant allergic inflammation.

SUBMITTER: Chen X 

PROVIDER: S-EPMC7190079 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature