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. TSP1KO 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.
Original language | English (US) |
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Pages (from-to) | 1293-1301 |
Number of pages | 9 |
Journal | Journal of Leukocyte Biology |
Volume | 94 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2013 |
Externally published | Yes |
Keywords
- Conjunctiva
- Corneal permeability
- Dry
- Eye
- Goblet cells
- IFN-γ
- Il-17A
- TGF-β
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Cell Biology