title: Dendritic cell-derived thrombospondin-1 is critical for the generation of the ocular surface Th17 response to desiccating stress.
abstract: TSP-1 is a physiologic activator of TGF-β, a critical induction factor for Th17-mediated immunity. The purpose of this study was to investigate the role of TSP-1 in the induction of the Th17 ocular surface response to DS. TSP-1KO and WT mice were subjected to DS5 and DS10), and parameters of ocular surface disease, including corneal barrier function, conjunctival CD4(+) T cell infiltration, and GC density, were evaluated. TSP-1KO mice subjected to DS had less corneal barrier disruption, reduced loss of PAS+ GC, and decreased CD4(+) T cell infiltration in the conjunctiva. In contrast to WT, TSP-1KO mice failed to up-regulate MMP-3 and MMP-9 mRNA transcripts in the cornea and IL-17A mRNA transcripts in the conjunctiva. RAG-1KO recipients of adoptively transferred CD4(+) T cells isolated from TSP-1KO mice subjected to DS5 showed milder dry-eye phenotype and less conjunctival inflammation than recipients of CD4(+) T cells from DS5 WT control. Reconstitution of TSP-1KO mice with WT DCs prior to DS reversed the resistance of the TSP-1KO to DS-induced immunopathology. In conclusion, DC-derived TSP-1 is critical for generating the Th17 ocular surface response to DS.
authors: 1.Baylor College of Medicine, 6565 Fannin St., NC 505, Houston, TX 77030, USA. cintiadp@bcm.tmc.edu.
authors: Niral B
authors: NB
authors: Gandhi
authors: Zhitao
authors: Z
authors: Su
authors: Xiaobo
authors: X
authors: Zhang
authors: Eugene A
authors: EA
authors: Volpe
authors: Flavia S A
authors: FS
authors: Pelegrino
authors: Salman A
authors: SA
authors: Rahman
authors: De-Quan
authors: DQ
authors: Li
authors: Stephen C
authors: SC
authors: Pflugfelder
authors: Cintia S
authors: CS
authors: de Paiva
mesh_terms: D000818:Animals; D003228:Conjunctiva / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003315:Cornea / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015352:Dry Eye Syndromes / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005136:Eye Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D013312:Stress, Physiological / Q000235:genetics / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019700:Thrombospondin 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; C585483:Thbs1 protein, mouse
keywords: IFN-γ; IL-17A; TGF-β; conjunctiva; corneal permeability; dry eye; goblet cells
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