September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A Novel Pollen/TLR4 Concept, an Innate Immunity Signaling Initiating IL-33/ST2 Pathways in Th2-dominant Allergic Inflammation
Author Affiliations & Notes
  • De-Quan Li
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • JIN LI
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
    School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China
  • Lili Zhang
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Xin Chen
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
    School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China
  • Stephen C Pflugfelder
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Xia Hua
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Fang Bian
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   De-Quan Li, None; JIN LI, None; Lili Zhang, None; Xin Chen, None; Stephen Pflugfelder, None; Xia Hua, None; Fang Bian, None
  • Footnotes
    Support  NIH NEI Grants EY023598 (DQL) and Core Grant for Vision Research EY-002520, Research to Prevent Blindness, Oshman Foundation, William Stamps Farish Fund.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      De-Quan Li, JIN LI, Lili Zhang, Xin Chen, Stephen C Pflugfelder, Xia Hua, Fang Bian; A Novel Pollen/TLR4 Concept, an Innate Immunity Signaling Initiating IL-33/ST2 Pathways in Th2-dominant Allergic Inflammation. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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

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Abstract

Purpose : Allergic diseases affect large population. Pollen, a ubiquitous allergen, is the trigger of seasonal rhinitis, conjunctivitis and asthma, as well as an exacerbating factor of atopic dermatitis. However, the underlying mechanism by which pollen induces interleukin 33 (IL-33) triggered allergic inflammation via epithelial innate immunity is largely unknown. This study was to explore whether short ragweed (SRW) pollen induces IL-33/ST2/Th2 allergic signaling via Toll-like receptor (TLR) 4-dependent pathways in allergic inflammation.

Methods : Three models were used for this study, a murine model of experimental allergic conjunctivitis (EAC) induced by SRW pollen, a topical challenge model on mouse ocular surface, and a culture model of primary human corneal epithelium exposed to aqueous extract of defatted SRW pollen (SRWe). Reverse transcription and quantitative real time PCR (RT-qPCR), ELISA and immunohistochemical and immunofluorescent staining were performed to evaluate the allergic signaling molecules.

Results : Acute topical challenge with SRW pollen generated a typical allergic conjunctivitis in SRW-sensitized BALB/c mice. Ocular allergic signs, stimulated mRNA and protein expression of IL-33 by corneal and conjunctival epithelia, and the infiltrated CD4+, ST2+ and IL1RAP+ cells with increased Th2 cytokines IL-4, IL-5 and IL-13 in conjunctiva and draining cervical lymph nodes showed strong evidence of EAC in BALB/c mice. However, All clinical and molecular changes were significantly reduced or eliminated in TLR4 deficient (Tlr4-d) or MyD88 knockout (MyD88-/-) mice, compared with their wild type littermates. SRWe directly stimulated IL-33 production by corneal and conjunctival epithelia in wild type, but not in Tlr4-d or MyD88-/- mice with a topical challenge model. Furthermore, SRWe-stimulated IL-33 mRNA and protein levels were also blocked by TLR4 neutralizing antibody and NF-kB inhibitor in mouse and human corneal epithelial cells.

Conclusions : These findings for the first time uncovered a novel mechanism by which SRW pollen, acting as a functional TLR4 agonist, initiates TLR4-dependent IL-33/ST2 signaling that triggers Th2-dominant allergic inflammation. These findings shed light on the understanding of mucosal epithelial innate immunity, and create new therapeutic targets to prevent and cure allergic diseases.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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