| First Author | Kim KH | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 8 | Pages | e0183678 |
| PubMed ID | 28837629 | Mgi Jnum | J:247323 |
| Mgi Id | MGI:5915085 | Doi | 10.1371/journal.pone.0183678 |
| Citation | Kim KH, et al. (2017) Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sjgren's syndrome. PLoS One 12(8):e0183678 |
| abstractText | PURPOSE: Extracellular high mobility group box 1 (HMGB1) acts as a damage associated molecular pattern molecule through the Toll-like receptor to promote autoreactive B cell activation, which may be involved in the pathogenesis of Sjgren's syndrome. The aim of this study was to investigate the effect of subconjunctival administration of anti-HMGB1 on dry eye in a mouse model of Sjgren's syndrome. METHODS: Ten weeks-old NOD.B10.H2b mice were subconjunctivally injected with 0.02 to 2 mug of anti-HMGB1 antibodies or PBS twice a week for two consecutive weeks. Tear volume and corneal staining scores were measured and compared between before- and after-treatment. Goblet cell density was counted in PAS stained forniceal conjunctiva and inflammatory foci score (>50 cells/focus) was measured in extraorbital glands. Flow cytometry was performed to evaluate the changes in BrdU+ cells, IL-17-, IL-10-, or IFNgamma-secreting cells, functional B cells, and IL-22 secreting innate lymphoid cells (ILC3s) in cervical lymph nodes. The level of IL-22 in intraorbital glands was measured by ELISA. RESULTS: Injection of 2 mug or 0.02 mug anti-HMGB1 attenuated corneal epithelial erosions and increased tear secretion (p<0.05). Goblet cell density was increased in 0.2 mug and 2 mug anti-HMGB1-treated-mice with marginal significance. The inflammatory foci score, and the number of BrdU+ cells, IL-17-, IL-10-, IFNgamma-secreting cells, and functional B cells did not significantly change following anti-HMGB1 treatment. Surprisingly, the percentage of ILC3s was significantly increased in the draining lymph nodes (p<0.05), and the expression of IL-22 was significantly increased in the intraorbital glands (p<0.05) after administration of 2 mug anti-HMGB1. CONCLUSION: This study shows that subconjunctival administration of anti-HMGB1 attenuates clinical manifestations of dry eye. The improvement of dry eye may involve an increase of ILC3s, rather than modulation of B or plasma cells, as shown using a mouse model of Sjgren's syndrome. |
