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10.1371/journal.pone.0183678

http://scihub22266oqcxt.onion/10.1371/journal.pone.0183678
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C5570279!5570279!28837629
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suck abstract from ncbi


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pmid28837629      PLoS+One 2017 ; 12 (8): ä
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  • Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sj?gren?s syndrome #MMPMID28837629
  • Kim KH; Kim DH; Jeong HJ; Ryu JS; Kim YJ; Oh JY; Kim MK; Wee WR
  • PLoS One 2017[]; 12 (8): ä PMID28837629show ga
  • 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.
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