Short ragweed pollen triggers allergic inflammation through Toll-like receptor 4–dependent thymic stromal lymphopoietin/OX40 ligand/OX40 signaling pathways - 30/11/11
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, Lili Zhang, MD a, b, , Stephen C. Pflugfelder, MD a, Cintia S. De Paiva, MD a, Xiaobo Zhang, MD a, Guiqiu Zhao, MD, PhD b, Xiaofen Zheng, MD a, Zhitao Su, MD a, Yangluowa Qu, MS aCorresponding author: De-Quan Li, MD, PhD, Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin St, NC-205, Houston, TX 77030.Abstract |
Background |
Allergic diseases affect a large population. Pollen, an 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 thymic stromal lymphopoietin (TSLP)–triggered allergic inflammation through epithelial innate immunity is largely unknown.
Objective |
We sought to explore whether short ragweed (SRW) pollen induces TSLP/OX40 ligand (OX40L)/OX40 signaling through Toll-like receptor (TLR) 4–dependent pathways in patients with allergic disease.
Methods |
Three models were used for this study, a well-characterized murine model of allergic conjunctivitis induced by SRW pollen, a topical challenge model on the murine ocular surface, and a culture model of primary human corneal epithelium exposed to aqueous extract of defatted SRW pollen (SRWe).
Results |
The topical challenges with SRW pollen generated typical allergic conjunctivitis in BALB/c mice. Clinical signs, stimulated TSLP/OX40L/OX40 signaling, and TH2 cytokine levels in the ocular mucosa and draining cervical lymph nodes were significantly reduced or eliminated in TLR4-deficient (Tlr4-d) or myeloid differentiation primary response gene 88 (MyD88) knockout (MyD88−/−) mice compared with those seen in their wild-type littermates. SRWe stimulated TSLP production by ocular epithelia in wild-type but not Tlr4-d or MyD88−/− mice. SRWe-stimulated TSLP was blocked by TLR4 antibody and nuclear factor κB inhibitor in murine and human corneal epithelia.
Conclusion |
For the first time, we have shown that SRW pollen, acting as a functional TLR4 agonist, initiates TLR4-dependent TSLP/OX40L/OX40 signaling, which triggers TH2-dominant allergic inflammation. These findings shed light on the understanding of mucosal epithelial innate immunity and create new therapeutic targets to cure allergic diseases.
Le texte complet de cet article est disponible en PDF.Key words : Allergy, pollen, conjunctivitis, Toll-like receptor, thymic stromal lymphopoietin, innate immunity
Abbreviations used : CLN, DC, EAC, HCEC, MyD88, NF-κB, OX40L, RT, SRW, SRWe, TLR, Tlr4-d, TSLP, TSLPR
Plan
| Supported by Department of Defense CDMRP PRMRP grant FY06 PR064719 (DQL), National Institutes of Health grant EY11915 (SCP), an unrestricted grant from Research to Prevent Blindness, the Oshman Foundation, and the William Stamps Farish Fund. |
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| Disclosure of potential conflict of interest: D.-Q. Li receives research support from the Department of Defense. S. C. Pflugfelder receives research support from the National Institutes of Health. The rest of the authors have declared that they have no conflict of interest. |
Vol 128 - N° 6
P. 1318 - décembre 2011 Retour au numéro
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