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Here we explore a novel pollen\/TLR4 innate immunity in allergic inflammation. In experimental allergic conjunctivitis induced by short ragweed (SRW) pollen, typical allergic signs, stimulated IL-33\/ST2 signaling and overproduced Th2 cytokine were observed in ocular surface, cervical lymph nodes and isolated CD4<jats:sup>+<\/jats:sup> T cells of BALB\/c mice. These clinical, cellular and molecular changes were significantly reduced\/eliminated in TLR4 deficient (<jats:italic>Tlr4-d<\/jats:italic>) or MyD88 knockout (<jats:italic>MyD88<\/jats:italic><jats:sup><jats:italic>\u2212<\/jats:italic>\/<jats:italic>\u2212<\/jats:italic><\/jats:sup>) mice. Aqueous SRW extract (SRWe) directly stimulated IL-33 mRNA and protein expression by corneal epithelium and conjunctiva in wild type, but not in <jats:italic>Tlr4-d<\/jats:italic> or <jats:italic>MyD88<\/jats:italic><jats:sup><jats:italic>\u2212<\/jats:italic>\/<jats:italic>\u2212<\/jats:italic><\/jats:sup> mice with topical challenge. Furthermore, SRWe-stimulated IL-33 production was blocked by TLR4 antibody and NF-kB inhibitor in mouse and human corneal epithelial cells. These findings for the first time uncovered a novel mechanism by which SRW pollen initiates TLR4-dependent IL-33\/ST2 signaling that triggers Th2-dominant allergic inflammation.<\/jats:p>","DOI":"10.1038\/srep36150","type":"journal-article","created":{"date-parts":[[2016,10,31]],"date-time":"2016-10-31T11:09:17Z","timestamp":1477912157000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Pollen\/TLR4 Innate Immunity Signaling Initiates IL-33\/ST2\/Th2 Pathways in Allergic Inflammation"],"prefix":"10.1038","volume":"6","author":[{"given":"Jin","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruzhi","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Pflugfelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Quan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,31]]},"reference":[{"key":"BFsrep36150_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/978-1-4419-0901-5_2","volume":"653","author":"S Bauer","year":"2009","unstructured":"Bauer, S., Muller, T. & Hamm, S. 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