Research Papers:

Leptin/OB-R pathway promotes IL-4 secretion from B lymphocytes and induces salivary gland epithelial cell apoptosis in Sjögren's syndrome

Ting Xu, Wen Xie, Yingchun Ma, Shiliang Zhou, Lu Zhang, Jinyun Chen, Mingyuan Cai, Rurong Sun, Peirong Zhang, Shaobo Yu, Zheng Xu, Wanlan Jiang and Min Wu _

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Oncotarget. 2017; 8:63417-63429. https://doi.org/10.18632/oncotarget.18823

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Ting Xu1, Wen Xie1, Yingchun Ma1, Shiliang Zhou1, Lu Zhang1, Jinyun Chen1, Mingyuan Cai1, Rurong Sun1, Peirong Zhang1, Shaobo Yu1, Zheng Xu1, Wanlan Jiang1 and Min Wu1

1Department of Rheumatology and Immunology, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou 213003, China

Correspondence to:

Min Wu, email: [email protected]

Keywords: Sjögren’s syndrome, SGECs, B lymphocytes, leptin, leptin receptor

Received: January 11, 2017     Accepted: June 01, 2017     Published: June 28, 2017


Sjögren's syndrome (SjS) is a chronic autoimmune epithelitis in which cell apoptosis promotes the formation of inflammatory lesions. We used immunohistochemistry and TUNEL to assay B cell infiltration and apoptosis in salivary gland tissue from 16-week-old NOD/LtJ mice with SjS. In co-cultures of primary salivary glandepithelial cells (SGECs) and spleen B cells, we assessed SGEC viability and apoptosis using CCK8 assays and flow cytometry. ELISAs were employed to assess cytokine levels in culture medium. Leptin protein, leptin receptor (OB-R), pro- and anti-apoptotic proteins, and Jak2/Stat3/ERK signaling molecules were analyzed using western blotting. B cell infiltration and salivary gland apoptosis were increased in salivary tissue from mice with SjS. Leptin treatment had no effect on cell viability or apoptosis among B cells and primary SGECs. B cell and SGEC co-culture systems showed that leptin increased apoptosis induced by B lymphocytes, reduced SGEC cell viability, and promoted IL-4 secretion from B cells. This suggests Leptin/OB-R signaling stimulates B cells-induced SGEC apoptosis via IL-4 secretion and OB-R-Jak2-Stat3 activation.

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