Effect of anti-high mobility group box 1 on innate lymphoid cells of dry eyes in mouse model of Sjögren syndrome (MUC2P.927)

Abstract

Abstract How innate lymphoid cells (ILCs) secrete cytokines is not well understood. High mobility group box (HMGB) may be involved in secreting IL17 or IL22 in ILCs. Extracellular HMGB1 may be related with the pathogenesis of Sjögren syndrome. We here investigated that administration of anti-HMGB1 might attenuate dry eyes by modulating ILCs in mouse model of Sjögren syndrome. This study was conducted in conformance with the FASEB Statement of Principles for the use of animals in research and education. 10 weeks-old NOD. B10 or B6 mice had been subconjunctivally injected by 0.02 to 2 ug of anti-HMGB1 antibodies or PBS for 2 weeks. Injection of anti-HMGB1 attenuated corneal epithelial erosions significantly by fluorescein staining and increased tear secretion transiently by phenol-red thread test. After stimulation of the cells from Peyer’s patches or cervical drainage lymph nodes by IL1b and IL23, cells were negatively gated using anti-mouse CD3-PerCP-Cy5.5 and B220-FITC, and were positively gated using anti-mouse CD45-APC-Cy7, NKp46-APC and IL22-PE. The percentages and the numbers of NKp46+IL22 or NKp46-IL22 secreting cells were increased in cervical lymph nodes of anti-HMGB1 injected mice compared with those in PBS injected mice. While, those were not significantly changed in Peyer’s patches of anti-HMGB1 or PBS injected mice. Together, data demonstrate that administration of anti-HMGB1 attenuates dry eyes by increasing IL-22-secreting ILCs in mouse model of Sjögren syndrome.