March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Short Ragweed Pollen Initiates TLR4-dependent TSLP/OX40L/OX40 Signaling Pathways in Experimental Allergic Conjunctivitis
Author Affiliations & Notes
  • De-Quan Li
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
  • Lili Zhang
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
    Department of Ophthalmology, The Affiliated Hospital of Qingdao University Medical College, Qingdao, China
  • Zhitao Su
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
    School of Optometry and Ophthalmology, Wenzhou Medical College, Wenzhou, China
  • Stephen C. Pflugfelder
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
  • Cintia S. De Paiva
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
  • Xiaobo Zhang
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
  • Footnotes
    Commercial Relationships  De-Quan Li, None; Lili Zhang, None; Zhitao Su, None; Stephen C. Pflugfelder, None; Cintia S. De Paiva, None; Xiaobo Zhang, None
  • Footnotes
    Support  DOD CDMRP PRMRP Grant FY06 PR064719 (DQL), NIH Grant EY11915 (SCP), Research to Prevent Blindness, Oshman Foundation, William Stamps Farish Fund.
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 4015. doi:
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      De-Quan Li, Lili Zhang, Zhitao Su, Stephen C. Pflugfelder, Cintia S. De Paiva, Xiaobo Zhang; Short Ragweed Pollen Initiates TLR4-dependent TSLP/OX40L/OX40 Signaling Pathways in Experimental Allergic Conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4015.

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

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Abstract

Purpose: : Pollen is the most common allergen that triggers seasonal conjunctivitis, rhinitis, and asthma, as well as exacerbates atopic dermatitis. However, the underlying mechanism by which pollen induces allergic inflammation via mucosal innate immunity is largely unknown. This study was to explore a novel insight that short ragweed (SRW) pollen initiates thymic stromal lymphopoietin (TSLP)/OX40L/OX40 signaling via Toll-like receptor (TLR) 4-dependent pathways in allergic conjunctivitis.

Methods: : A murine model of experimental allergic conjunctivitis (EAC) was induced in BALB/c, TLR4 deficient, MyD88 wild type and knockout mice by multiple daily topical challenges with SRW pollen after sensitized with SRW injected in footpad for 10 days. The mice without treatment or with topically applied PBS were used as controls. The blood, corneal epithelium, conjunctiva, and cervical lymph nodes were collected after treatment. The mRNA expression was determined by reverse transcription and real time PCR with TaqMan primers and probes. The protein production was measured by immunohistochemical staining, and serum SRW-specific IgE was measured by ELISA.

Results: : Repeated topical challenges with SRW allergen generated typical clinical signs that mimic human allergic conjunctivitis in sensitized BALB/c mice with markedly induced levels of SRW-specific IgE in the serum. The increased TSLP expression and production were observed in corneal and conjunctival epithelia, where dendritic cells that produce OX40L, and Th2 cells that produce OX40, IL-4, IL-5 and IL-13, largely infiltrated. Interestingly, the clinical signs, induced SRW-specific IgE in serum, and stimulated TSLP/OX40L/OX40 signaling and Th2 cytokines in ocular mucosa and draining cervical lymph nodes were significantly reduced or eliminated in TLR4 deficient or MyD88 knockout mice, compared with their wild type littermates.

Conclusions: : We for the first time uncovered a novel phenomenon that SRW pollen, acting as a functional TLR4 agonist, initiates TLR4-dependent TSLP/OX40L/OX40 signaling that triggers Th2-dominant allergic inflammation. These findings shed light on the understanding of mucosal epithelial innate immunity, and may create new therapeutic targets to cure allergic diseases.

Keywords: conjunctivitis • cornea: epithelium • cytokines/chemokines 
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