Autoimmune rheumatologic diseases

Poster

Local Administration of Anti-high Mobility Group Box 1 Attenuates Dry Eyes in a Mouse Model of Sjögren’s Syndrome

Friday, June 16
6:15 PM - 7:30 PM

Purpose: Extracellular high mobility group box 1 (HMGB1) acts as a damage associated molecular pattern (DAMP) molecule, which may be involved in the pathogenesis of Sjögren syndrome. Therefore, we aimed to investigate effect of subconjunctival administration of anti-HMGB1 on dry eyes in a mouse model of Sjögren's syndrome.


Methods: 0.02 to 2 μg of anti-HMGB1 antibodies or PBS were injected subconjunctivally into 10 week-old NOD.B10.H2b mice twice a week for 2 weeks. Tear volume and corneal staining scores were measured after treatment. Goblet cell density was counted in PAS stained forniceal conjunctiva and inflammatory foci score was measured in extraorbital glands. The changes of BrdU+ cells, IL17-, IL10- or IFNγ-secreting cells, functional B cells, and IL-22 secreting innate lymphoid cells (ILCs) were evaluated in cervical lymph nodes. The level of IL-22 was measured in intraorbital glands.


Results: Injection of 2 μg anti-HMGB1 attenuated corneal epithelial erosions and increased tear secretion and goblet cell density. However, the inflammatory foci score, and the number of BrdU+ T or B cells, IL-17-, IL-10-, IFNγ-secreting cells, and functional B cells were not changed. On the other hands, the percentages of IL-22 secreting ILCs was significantly increased in draining lymph nodes and the expression of IL-22 was significantly increased in intraorbital glands with 2 μg of anti-HMGB1 administration.


Conclusion: This study suggests that subconjunctival administration of anti-HMGB1 attenuate clinical manifestations of dry eye by increasing IL-22-secreting ILCs, rather than modulating B or plasma cells, in a mouse model of Sjögren's syndrome.

MEE KUM KIM

Seoul National University Hospital

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    Hyun Jeong Jeong

    Laboratory of Ocular Regenerative Medicine and Immunology, Artificial Eye Center, Seoul National University Hospital Biomedicall Research Institute

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      Jin Suk Ryu

      Laboratory of Ocular Regenerative Medicine and Immunology, Artificial Eye Center, Seoul National University Hospital Biomedicall Research Institute

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        Yu Jeong Kim

        Seoul National University Hospital

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          Joo Youn Oh

          Seoul National University Hospital

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            Won Ryang Wee

            Seoul National University Hospital

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              Local Administration of Anti-high Mobility Group Box 1 Attenuates Dry Eyes in a Mouse Model of Sjögren’s Syndrome



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