Xin Chen1,2, Ruzhi Deng1,2, Wei Chi2,3, Xia Hua2, Fan Lu1, Fang Bian2, Ning Gao2, Zhijie Li4, Stephen C Pflugfelder2, Cintia S de Paiva2, De-Quan Li2. 1. School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China. 2. Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas. 3. Zhongshan Ophthalmic Center, Sun Yan-Sen University, Guangzhou, China. 4. Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
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.
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-/- -EACmice. 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.
Authors: Jin Li; Xia Hua; Lili Zhang; Fan Lu; Terry G Coursey; Stephen C Pflugfelder; De-Quan Li Journal: Sci Rep Date: 2016-01-14 Impact factor: 4.379
Authors: Ruzhi Deng; Xin Chen; Yun Zhang; Fang Bian; Ning Gao; Jiaoyue Hu; Changjun Wang; Rodrigo G de Souza; Fan Lu; Stephen C Pflugfelder; De-Quan Li Journal: Mucosal Immunol Date: 2019-07-26 Impact factor: 7.313
Authors: Ivan V Bogdanov; Ekaterina I Finkina; Daria N Melnikova; Rustam H Ziganshin; Tatiana V Ovchinnikova Journal: Nutrients Date: 2021-06-16 Impact factor: 5.717
Authors: Cintia S de Paiva; Claudia M Trujillo-Vargas; Laura Schaefer; Zhiyuan Yu; Robert A Britton; Stephen C Pflugfelder Journal: Front Immunol Date: 2021-07-19 Impact factor: 7.561