Dataset Information

Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sj?gren's syndrome.

ABSTRACT:

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 Sj?gren'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 Sj?gren's syndrome.

Methods

Ten weeks-old NOD.B10.H2b mice were subconjunctivally injected with 0.02 to 2 ?g 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 IFN?-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 ?g or 0.02 ?g anti-HMGB1 attenuated corneal epithelial erosions and increased tear secretion (p<0.05). Goblet cell density was increased in 0.2 ?g and 2 ?g anti-HMGB1-treated-mice with marginal significance. The inflammatory foci score, and the number of BrdU+ cells, IL-17-, IL-10-, IFN?-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 ?g 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 Sj?gren's syndrome.

SUBMITTER: Kim KH

PROVIDER: S-EPMC5570279 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sjӧgren's syndrome.

Kim Kyeong Hwan KH Kim Dong Hyun DH Jeong Hyun Jeong HJ Ryu Jin Suk JS Kim Yu Jeong YJ Oh Joo Youn JY Kim Mee Kum MK Wee Won Ryang WR

PloS one 20170824 8

<h4>Purpose</h4>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 Sjӧgren'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 Sjӧgren's syndrome.<h4>Methods</h4>Ten weeks-old NOD.B10.H2b mice were subconjunctivally injected with 0.02 to ...[more]

PMID: 28837629

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