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IL ‐27 signaling deficiency develops Th17‐enhanced Th2‐dominant inflammation in murine allergic conjunctivitis model
Author(s) -
Chen Xin,
Deng Ruzhi,
Chi Wei,
Hua Xia,
Lu Fan,
Bian Fang,
Gao Ning,
Li Zhijie,
Pflugfelder Stephen C.,
Paiva Cintia S.,
Li DeQuan
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13691
Subject(s) - thymic stromal lymphopoietin , allergic inflammation , immunology , foxp3 , inflammation , cytokine , rar related orphan receptor gamma , conjunctiva , allergic conjunctivitis , interleukin , blot , medicine , immune system , biology , allergy , biochemistry , gene
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, C57 BL /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 ( CLN s) 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 C57 BL /6 mice. The decrease of IL ‐27 at mRNA ( IL ‐27/ EBI 3) 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 γt. In contrast, Th1 cytokine IFN γ and Treg marker IL ‐10, with their respective transcription factors T‐bet and foxp3, were largely suppressed. Interestingly, imbalanced activation between reduced phosphor (P)‐ STAT 1 and stimulated P‐ STAT 6 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.