A detrimental effect of interleukin-22 on salivary gland tissue integrity and function

Abstract

Abstract Interleukin-22 (IL-22) has well-documented effects in promoting epithelial wound healing and protecting tissue damage in the intestine and lung. However, in certain inflammatory diseases such as psoriasis, IL-22 can also exert tissue-detrimental effect. Although the up-regulation of IL-22 has been reported in patients with Sjögren’s syndrome (SS), the role of IL-22 in this disease is not well-characterized. Herein, we investigated the effects of IL-22 on SS-like salivary gland disorder using both in vivo and in vitro approaches. To assess the effects of exogenous IL-22 on salivary gland tissues in vivo, IL-22 was directly injected into submandibular glands (SMGs) of 7–12 weeks old female C57BL/6 and the non-obese diabetic (NOD) mice, a model of SS disease. The salivary flow rate was decreased and the caspase-3 level was increased in the SMGs of the IL-22-treated C57BL/6 mice. IL-22 treatment also decreased the salivary flow rate and increased the level of capase-3 in the SMGs in the NOD mice. We determined the effects of endogenous IL-22 using an anti-CD3 antibody-induced acute exocrinopathy model. Anti-CD3 antibody was intraperitoneally injected into 8-week-old female C57BL/6 mice every other day for 3 days, together with a neutralizing anti-IL-22 antibody or its isotype control IgG. Neutralization of endogenous IL-22 improved saliva production and reduced caspase-3 activation in the SMGs in anti-CD3-treated C57BL/6 mice. Moreover, in vitro IL-22 treatment of a human salivary gland epithelial cells induced STAT3 activation and inhibited cell expansion. Taken together, these results provided strong evidence that IL-22 can directly act on salivary gland epithelial cells and promote damage and dysfunction of salivary gland tissues.