Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sjӧgren's syndrome.
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 o...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5570279?pdf=render |
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| author | Kyeong Hwan Kim Dong Hyun Kim Hyun Jeong Jeong Jin Suk Ryu Yu Jeong Kim Joo Youn Oh Mee Kum Kim Won Ryang Wee |
| author_facet | Kyeong Hwan Kim Dong Hyun Kim Hyun Jeong Jeong Jin Suk Ryu Yu Jeong Kim Joo Youn Oh Mee Kum Kim Won Ryang Wee |
| author_sort | Kyeong Hwan Kim |
| collection | DOAJ |
| description | 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.Ten weeks-old NOD.B10.H2b mice were subconjunctivally injected with 0.02 to 2 μg 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 IFNγ-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.Injection of 2 μg or 0.02 μg anti-HMGB1 attenuated corneal epithelial erosions and increased tear secretion (p<0.05). Goblet cell density was increased in 0.2 μg and 2 μg anti-HMGB1-treated-mice with marginal significance. The inflammatory foci score, and the number of BrdU+ cells, IL-17-, IL-10-, IFNγ-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 μg anti-HMGB1.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 Sjӧgren's syndrome. |
| first_indexed | 2024-12-11T18:10:11Z |
| format | Article |
| id | doaj.art-b741d5225c6a48ecaf227f7f4c1c435c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T18:10:11Z |
| publishDate | 2017-01-01 |
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| spelling | doaj.art-b741d5225c6a48ecaf227f7f4c1c435c2022-12-22T00:55:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018367810.1371/journal.pone.0183678Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sjӧgren's syndrome.Kyeong Hwan KimDong Hyun KimHyun Jeong JeongJin Suk RyuYu Jeong KimJoo Youn OhMee Kum KimWon Ryang WeeExtracellular 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.Ten weeks-old NOD.B10.H2b mice were subconjunctivally injected with 0.02 to 2 μg 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 IFNγ-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.Injection of 2 μg or 0.02 μg anti-HMGB1 attenuated corneal epithelial erosions and increased tear secretion (p<0.05). Goblet cell density was increased in 0.2 μg and 2 μg anti-HMGB1-treated-mice with marginal significance. The inflammatory foci score, and the number of BrdU+ cells, IL-17-, IL-10-, IFNγ-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 μg anti-HMGB1.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 Sjӧgren's syndrome.http://europepmc.org/articles/PMC5570279?pdf=render |
| spellingShingle | Kyeong Hwan Kim Dong Hyun Kim Hyun Jeong Jeong Jin Suk Ryu Yu Jeong Kim Joo Youn Oh Mee Kum Kim Won Ryang Wee Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sjӧgren's syndrome. PLoS ONE |
| title | Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sjӧgren's syndrome. |
| title_full | Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sjӧgren's syndrome. |
| title_fullStr | Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sjӧgren's syndrome. |
| title_full_unstemmed | Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sjӧgren's syndrome. |
| title_short | Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sjӧgren's syndrome. |
| title_sort | effects of subconjunctival administration of anti high mobility group box 1 on dry eye in a mouse model of sjӧgren s syndrome |
| url | http://europepmc.org/articles/PMC5570279?pdf=render |
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