Low-dose interleukin-2 can improve salivary secretion but not lymphocyte infiltration of salivary glands in a murine model of Sjögren’s syndrome

• Published in: BMC immunology 2022-10, Vol.23 (1), p.1-49, Article 49
• Main Authors: Wen, Junsong, Zhu, Fenglin, Yu, Xi, Xie, Hualing, Li, Chengyin
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Care and treatment; CD8 antigen; Cell proliferation; Chemokines; Cloning; Cytokines; Diabetes mellitus; Diagnosis; Disease; Distribution; Drug dosages; Exocrine function; Exocrine glands; Flow cytometry; Immune system; Immune-related damage; Immunoassay; Infiltration; Interleukin 2; Interleukins; Lupus; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Medical examination; Medical research; Methods; Pathogenesis; Salivary diagnostics; Salivary gland; Salivary glands; Sjogren's syndrome; Sjögren’s syndrome; Structure-function relationships; Submandibular gland
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/s12865-022-00524-1

Effects of low-dose interleukin-2 (IL-2) on the exocrine glandular glands of Sjögren's syndrome are unknown. The aim of this study was to investigate the effects of low-dose IL-2 on salivary gland structure and function in a murine model of Sjögren's syndrome. Non-obese diabetic/Ltj (NOD) mice were used as the animal model of Sjögren's syndrome, and low-dose IL-2 or phosphate buffered saline was administered subcutaneously from 5 weeks of age, while ICR mice were used as controls. Some mice were sacrificed at 9 weeks of age, while the other mice that continued to receive treatment were sacrificed at 23 weeks. We determined the salivary flow rate of mice every 3 weeks during the intervention. After the mice were sacrificed, one submandibular gland was removed for pathological evaluation, while the other submandibular gland was used to measure the levels of 25 cytokines by Luminex technology. Cervical lymph nodes and spleens were examined by flow cytometry for the proportions of CD8.sup.+ T cells and Treg cells. The results showed that the salivary flow rate of NOD mice was slower than that of control-group mice, and there were more pathological changes in the submandibular gland. The levels of many cytokines in the submandibular gland were elevated. The proportion of CD8.sup.+ T cells in the cervical lymph nodes and spleens was increased; however, the proportion of Treg cells was decreased. After treatment with IL-2, the exocrine function of the salivary glands of mice was improved. IL-2 also promoted the proliferation of Treg cells in the cervical lymph nodes and spleens, but it did not alter the extent of lymphocyte infiltration in the submandibular gland. The levels of cytokines in the submandibular glands, as well as the proportion of CD8.sup.+ T cells in the cervical lymph nodes and spleens, were unchanged significantly after IL-2 treatment. Our results demonstrate that treatment with low-dose IL-2 improves the secretory function of the exocrine glands of mice with Sjögren's syndrome, but it does not reverse the structural damage of the exocrine glands.