July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Suppressed Interleukin-27 Signaling Aggravates Pollen-induced Allergic Inflammation via T Cell Dysregulation by Imbalanced STAT1/STAT6 Activation
Author Affiliations & Notes
  • De-Quan Li
    Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • XIN Chen
    Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
    School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China
  • Stephen C Pflugfelder
    Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Ruzhi Deng
    Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
    School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China
  • Xia Hua
    Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Wenjuan Qin
    Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Ning Gao
    Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   De-Quan Li, None; XIN Chen, None; Stephen Pflugfelder, None; Ruzhi Deng, None; Xia Hua, None; Wenjuan Qin, None; Ning Gao, None
  • Footnotes
    Support  NIH NEI Grants EY023598 (DQL) and EY011915 (SCP), Core Grant for Vision Research EY002520, Research to Prevent Blindness, Oshman Foundation, William Stamps Farish Fund.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3314. doi:
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    • Get Citation

      De-Quan Li, XIN Chen, Stephen C Pflugfelder, Ruzhi Deng, Xia Hua, Wenjuan Qin, Ning Gao; Suppressed Interleukin-27 Signaling Aggravates Pollen-induced Allergic Inflammation via T Cell Dysregulation by Imbalanced STAT1/STAT6 Activation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3314.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The protective role of immunosuppressive cytokines in allergic inflammation is not clear. This study was to explore a novel molecular mechanism by which pollen triggers allergic inflammation through suppressing IL-27 anti-inflammatory signaling pathway.

Methods : A murine model of experimental allergic conjunctivitis (EAC) was induced in BALB/c or IL-27Rα deficient (WSX-1-/-) mice by short ragweed (SRW) pollen, with untreated or PBS-treated mice as controls. The serum, eyeballs, conjunctiva, cervical lymph nodes (CLN), CLN cells and bone marrow-derived dendritic cells (DCs) were used for study. Gene expression was determined by RT-qPCR, protein production and activation were evaluated by immunostaining, ELISA and Western blotting.

Results : Typical allergic manifestations and stimulated TSLP signaling and Th2 responses were observed in ocular surface of BALB/c-EAC mice induced by SRW. 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. Furthermore, SRW pollen was identified to suppress IL-27 expression in CLN cells ex vivo, and DCs in vitro.

Conclusions : Our findings for the first time uncovered a novel mechanism by which SRW pollen triggers allergic inflammation via suppressing IL-27 anti-allergic signaling pathway, resulting in T cell dysregulation with imbalanced activation of STAT1/STAT6. The findings provide a new understanding on allergic pathogenesis and the therapeutic potential to treat allergic diseases.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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