title: Pollen/TLR4 Innate Immunity Signaling Initiates IL-33/ST2/Th2 Pathways in Allergic Inflammation.
abstract: Innate immunity has been extended to respond environmental pathogen other than microbial components. 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+T cells of BALB/c mice. These clinical, cellular and molecular changes were significantly reduced/eliminated in TLR4 deficient (Tlr4-d) or MyD88 knockout (MyD88-/-) mice. Aqueous SRW extract (SRWe) directly stimulated IL-33 mRNA and protein expression by corneal epithelium and conjunctiva in wild type, but not in Tlr4-d or MyD88-/-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.
authors: School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China.|Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors: Jin
authors: J
authors: Li
authors: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors: Lili
authors: L
authors: Zhang
authors: School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China.|Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors: Xin
authors: X
authors: Chen
authors: School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China.|Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors: Ding
authors: D
authors: Chen
authors: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors: Xia
authors: X
authors: Hua
authors: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors: Fang
authors: F
authors: Bian
authors: School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China.
authors: Ruzhi
authors: R
authors: Deng
authors: School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China.
authors: Fan
authors: F
authors: Lu
authors: Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors: Zhijie
authors: Z
authors: Li
authors: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors: Stephen C
authors: SC
authors: Pflugfelder
authors: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors: De-Quan
authors: DQ
authors: Li
mesh_terms: D000328:Adult; D000818:Animals; D052179:Antigens, Plant / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000235:genetics / Q000378:metabolism*; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010936:Plant Extracts / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D015398:Signal Transduction; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D052179:Antigens, Plant; D016207:Cytokines; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D010936:Plant Extracts; D051197:Toll-Like Receptor 4; C433085:ragweed pollen