NDLI: Desiccating stress promotion of Th17 differentiation by ocular surface tissues through a dendritic cell-mediated pathway.

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Desiccating stress promotion of Th17 differentiation by ocular surface tissues through a dendritic cell-mediated pathway.

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Desiccating stress promotion of Th17 differentiation by ocular surface tissues through a dendritic cell-mediated pathway.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Pflugfelder, Stephen C. Zheng, Xiaofen Li, De-Quan de Paiva, Cintia S. Farley, William J.
Description	Country affiliation: United States Author Affiliation: Zheng X ( Department of Ophthalmology, Baylor College of Medicine, Ocular Surface Center, Cullen Eye Institute, Houston, Texas 77030, USA.)
Abstract	PURPOSE: To explore the phenomenon that corneal and conjunctival tissues subjected to desiccating stress (DS) promote Th17 differentiation by stimulating the production of Th17-inducing cytokines through a dendritic cell (DC)-mediated pathway. METHODS: Experimental dry eye was created by subjecting C57BL/6 mice to desiccating environmental stress. Corneal and conjunctival explants from dry eye or control mice were cocultured with DCs for 24 hours before CD4(+) T cells were added for an additional 4 to 7 days. Expression of Th17-associated genes in the cornea, conjunctiva, DCs, and CD4(+) T cells was evaluated by real-time PCR. Cytokine concentrations in coculture supernatants were measured by immunobead assay. IL-17-producing T cells were identified by ELISPOT bioassay. RESULTS: Higher levels of IL-17A, TGF-beta1, TGF-beta2, IL-6, IL-23, and IL-1beta mRNA transcripts and TGF-beta1, IL-6, and IL-1beta protein were observed in corneal epithelium and conjunctiva from dry eye mice. DCs cocultured with epithelial explants from dry eye mice for 2 days produced higher levels of TGF-beta1, IL-6, IL-23, and IL-1beta mRNA transcripts and of TGF-beta1, IL-6, and IL-1beta protein. CD4(+) T cells cocultured with DCs and epithelial explants from dry eye mice expressed increased levels of IL-17A, IL-17F, IL-22, CCL-20, and retinoic acid receptor-related orphan receptor-gammat mRNA transcripts and increased IL-17A protein and number of IL-17-producing T cells (Th17 cells). CONCLUSIONS: These findings demonstrate that DS creates an environment on the ocular surface that stimulates the production of Th17-inducing cytokines by corneal and conjunctival epithelia that promote Th17 differentiation through a dendritic cell-mediated pathway.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.09-3838
Journal	Investigative Opthalmology & Visual Science
Issue Number	6
Volume Number	51
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2010-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Differentiation Conjunctiva Metabolism Cornea Dendritic Cells Physiology Dry Eye Syndromes Interleukin-17 Genetics T-lymphocytes, Helper-inducer Immunology Animals Bone Marrow Cells Cd4-positive T-lymphocytes Coculture Techniques Desiccation Disease Models, Animal Chemically Induced Enzyme-linked Immunosorbent Assay Epithelial Cells Flow Cytometry Gene Expression Immunoenzyme Techniques Mice Mice, Inbred C57bl Reverse Transcriptase Polymerase Chain Reaction Scopolamine Hydrobromide Toxicity Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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