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Interleukin-22 Exerts Detrimental Effects on Salivary Gland Integrity and Function.

Jing Zhou | Shoko Onodera | Yang Hu | Qing Yu
International journal of molecular sciences | 2022

Interleukin-22 (IL-22) affects epithelial tissue function and integrity in a context-dependent manner. IL-22 levels are elevated in salivary glands of Sjögren's syndrome (SS) patients, but its role in the pathogenesis of this disease remains unclear. The objective of this study is to elucidate the impact of IL-22 on salivary gland tissue integrity and function in murine models. We showed that IL-22 levels in sera and salivary glands increased progressively in female non-obese diabetic (NOD) mice, accompanying the development of SS. Administration of IL-22 to the submandibular glands of NOD mice prior to the disease onset reduced salivary secretion and induced caspase-3 activation in salivary gland tissues, which were accompanied by alterations in multiple genes controlling tissue integrity and inflammation. Similarly, IL-22 administration to submandibular glands of C57BL/6 mice also induced hyposalivation and caspase-3 activation, whereas blockade of endogenous IL-22 in C57BL/6 mice treated with anti-CD3 antibody mitigated hyposalivation and caspase-3 activation. Finally, IL-22 treatment reduced the number of viable C57BL/6 mouse submandibular gland epithelial cells cultured in vitro, indicating a direct impact of this cytokine on these cells. We conclude that IL-22 exerts a detrimental impact on salivary gland tissues.

Pubmed ID: 36361787

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R03 AI142273
  • Agency: NIH HHS, United States
    Id: R03 AI142273, R01 DE023838, R56 DE023838,R03 DE028033, R01 DE030646
  • Agency: NIDCR NIH HHS, United States
    Id: R03 DE028033
  • Agency: NIDCR NIH HHS, United States
    Id: R56 DE023838
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE023838
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE030646

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