Dataset Information
IL-27 signaling deficiency develops Th17-enhanced Th2-dominant inflammation in murine allergic conjunctivitis model.
Ontology highlight
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-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, 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 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.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
Publications
IL-27 signaling deficiency develops Th17-enhanced Th2-dominant inflammation in murine allergic conjunctivitis model.
Allergy 20190104 5
<h4>Background</h4>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.<h4>Methods</h4>A murine model of experimental allergic conjunctivitis (EAC) was induced in BALB/c, C57BL/6 or IL-27Rα-deficient (WSX-1<sup>-/-</sup> ) mice by short ragweed pollen, with untreated or PBS-t ...[more]