June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Suppressed Signaling of Interleukine 27, a Novel Immunosuppressive Cytokine, in Experimental Allergic Conjunctivitis Induced by Short Ragweed Pollen
Author Affiliations & Notes
  • XIN CHEN
    OPHTHALMOLOGY, BAYLOR COLLEGE OF MEDICINE, Houston, Texas, United States
    School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • Wei Chi
    OPHTHALMOLOGY, BAYLOR COLLEGE OF MEDICINE, Houston, Texas, United States
    Zhongshan Ophthalmic Center, Sun Yan-Sen University, Guangzhou, Guangdong, China
  • Changjun Wang
    OPHTHALMOLOGY, BAYLOR COLLEGE OF MEDICINE, Houston, Texas, United States
  • Zhao Liu
    OPHTHALMOLOGY, BAYLOR COLLEGE OF MEDICINE, Houston, Texas, United States
  • Xia Hua
    OPHTHALMOLOGY, BAYLOR COLLEGE OF MEDICINE, Houston, Texas, United States
  • Ruzhi Deng
    OPHTHALMOLOGY, BAYLOR COLLEGE OF MEDICINE, Houston, Texas, United States
    School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • Fang Bian
    OPHTHALMOLOGY, BAYLOR COLLEGE OF MEDICINE, Houston, Texas, United States
  • Stephen C Pflugfelder
    OPHTHALMOLOGY, BAYLOR COLLEGE OF MEDICINE, Houston, Texas, United States
  • De-Quan Li
    OPHTHALMOLOGY, BAYLOR COLLEGE OF MEDICINE, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   XIN CHEN, None; Wei Chi, None; Changjun Wang, None; Zhao Liu, None; Xia Hua, None; Ruzhi Deng, None; Fang Bian, None; Stephen Pflugfelder, None; De-Quan Li, 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 June 2017, Vol.58, 5756. doi:
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    • Get Citation

      XIN CHEN, Wei Chi, Changjun Wang, Zhao Liu, Xia Hua, Ruzhi Deng, Fang Bian, Stephen C Pflugfelder, De-Quan Li; Suppressed Signaling of Interleukine 27, a Novel Immunosuppressive Cytokine, in Experimental Allergic Conjunctivitis Induced by Short Ragweed Pollen. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5756.

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

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Abstract

Purpose : While most studies focused on pro-allergic cytokines, the protective role of immunosuppressive cytokines in allergic inflammation is largely unknown. This study was to explore a novel anti-inflammatory role and molecular mechanism of IL-27 in allergic inflammation induced by short ragweed pollen.

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, which was first immunized with 50µg in 5 mg Imject Alum by footpad injection on day 1, followed by topical challenge of 1.5mg SRW in 10µl PBS into each eye once a day from days 11 to 13. Mice without treatment (UT) or treated with PBS along will be used as controls. The serum, eyeballs, conjunctiva and cervical lymph nodes (CLN) were collected on days 14 for evaluation. The mRNA expression was determined by RT-qPCR. The protein production was evaluated by immunostaining, ELISA, Western blotting and/or flow cytometry.

Results : Typical allergic signs, stimulated TSLP signaling and Th2 cytokine overproduction were observed in ocular surface of BALB/c mice with EAC induced by SRW. The decrease of IL-27 at mRNA (IL-27A/EBI3 two chains) and protein levels, accompanied by suppressed levels of IL-10 and signaling molecules STAT1, C-Maf, ICOS and PD-L1 with increased STAT6 and GATA3, was observed in conjunctiva and draining CLN tissues of SRW-EAC mice when compared with UT or PBS control mice, as evaluated by RT-qPCR, immunofluorescent staining, ELISA and/or Western blotting. IL-27 was identified to be produced mainly by dendritic cells (DCs) and macrophages, but not epithelial or T cells by flow cytometry and immunostaining with specific cell surface markers CD11c, F4/80 and CD4. Furthermore, EAC model induced by SRW in WSX-1-/- mice showed more severe allergic signs with significantly higher expression of TSLP by corneal and conjunctival epithelial cells, OX40L by DCs, and Th2 cytokines IL-4, IL-5 and IL-13 by CD4+ T cells than EAC-BALB/c mice.

Conclusions : Our findings for the first time uncovered a novel mechanism by which SRW pollen triggers Th2-dominant allergic inflammation by suppressing IL-27 anti-allergic signaling pathway. These findings shed light on the understanding of pollen-induced allergic inflammation, and may create new therapeutic targets to treat allergic diseases.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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