Purchase this article with an account.
Lili Zhang, Xiaofen Zheng, Guiqiu Zhao, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li; TLR4/MyD88 Innate Immunity Pathway Mediates TSLP/IL-33 Triggered Inflammation in Murine Allergic Conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2913.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Thymic stromal lymphopoietin (TSLP) and Interleukin (IL) 33 have been recently identified as two novel epithelium-derived pro-allergic cytokines that initiate Th2-dominant allergic inflammation. This study was to explore the role of toll-like receptor (TLR) 4 and MyD88 innate immune pathway in TSLP/IL-33 triggered allergic inflammation in murine experimental allergic conjunctivitis (EAC).
An EAC model was induced in BALB/c, TLR4 deficient (Tlr4-d), MyD88 wild type (MyD88+/+) and knockout (Myd88-/-) mice by multiple daily topical challenges with short ragweed (SRW) pollen after sensitization with SRW pollen injected in the hind footpad for 10 days. The mice without treatment or with topically applied PBS were used as controls. The 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.
In the SRW pollen induced EAC BALB/c mice, we observed significantly increased TSLP and IL-33 mRNA expression and immunoreactivity in the corneal and conjunctival epithelia. CD11c+/OX40L+ dendritic cells and CD4+/ST2+ Th2 cells largely infiltrated the conjunctiva. The increased mRNA levels of TSLP downstream molecules (TSLPR, OX40L and OX40), IL-33 receptor ST2, and Th2 cytokines (IL-4, IL-5 and IL-13) were detected in the corneal epithelia, conjunctiva and cervical lymph nodes. Interestingly, the ocular allergic signs and stimulated production of TSLP, IL-33, OX40L and ST2, as well as Th2 cytokines by ocular mucosa, especially conjunctiva tissues, were dramatically reduced or eliminated in BALB/c based Tlr4-d mice. The clinical signs, TSLP/IL-33 signaling and Th2 dominant inflammation were also significantly attenuated in C57BL/6 based MyD88-/- mice, when compared with paired MyD88+/+ mice challenged by SRW pollen.
These findings demonstrate that epithelium-derived pro-allergic cytokines TSLP and IL-33 trigger the allergic inflammation through OX40L-OX40 and IL-33-ST2 signaling pathways, which are mediated by TLR4/MyD88 innate immune pathway in ocular mucosal surface.
This PDF is available to Subscribers Only