International immunopharmacology · 2023
MANF inhibits Sjögren's syndrome salivary gland epithelial cell apoptosis and antigen expression of Ro52/SSA through endoplasmic reticulum stress/autophagy pathway.
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Cheng Danqian, Zhou Tongtong, Liu Hui, Li Lijun, Xuan Yuhao, Huang Lijun, Liu Yuqi, Zhang Xiao, Wei Wei, Wu Huaxun
Аннотация
BACKGROUND: Sjögren's syndrome (SS) is a typical autoimmune disease characterized by lymphocyte infiltration accompanied by the production of Ro52/SSA and La/SSB autoantibodies against whole body ribonucleoprotein particles. The release of type I IFN can induce endoplasmic reticulum stress (ERS) in submandibular gland cells. ERS not only produces a large number of Ro52/SSA antigens and changes their location, but also down-regulates autophagy and increases apoptosis.
METHOD: We collected human submandibular gland tissue samples, established an Experimental Sjögren's syndrome (ESS) mouse model, and used submandibular gland cells to test whether Mesencephalic astrocyte-derived neurotrophic factor (MANF) could reverse ERS-induced autophagy downregulation and reduce apoptosis and Ro52/SSA antigen expression.
RESULT: It was found that MANF could reduce lymphocyte infiltration and the proportion of CD4+ T cell subsets in the salivary glands, reduce the phosphorylation of AKT and mTOR proteins and the expression of ERS-related proteins, and increase the expression of autophagy proteins. We also found that MANF can reduce the expression of Ro52/SSA antigen on the cell membrane and reduce apoptosis.
CONCLUSION: In short, we found that MANF can activate autophagy, inhibit apoptosis and reduce the expression of Ro52/SSA by regulating the AKT/mTOR/LC3B signaling pathway. The above results suggest that MANF may be a protective factor against SS.
METHOD: We collected human submandibular gland tissue samples, established an Experimental Sjögren's syndrome (ESS) mouse model, and used submandibular gland cells to test whether Mesencephalic astrocyte-derived neurotrophic factor (MANF) could reverse ERS-induced autophagy downregulation and reduce apoptosis and Ro52/SSA antigen expression.
RESULT: It was found that MANF could reduce lymphocyte infiltration and the proportion of CD4+ T cell subsets in the salivary glands, reduce the phosphorylation of AKT and mTOR proteins and the expression of ERS-related proteins, and increase the expression of autophagy proteins. We also found that MANF can reduce the expression of Ro52/SSA antigen on the cell membrane and reduce apoptosis.
CONCLUSION: In short, we found that MANF can activate autophagy, inhibit apoptosis and reduce the expression of Ro52/SSA by regulating the AKT/mTOR/LC3B signaling pathway. The above results suggest that MANF may be a protective factor against SS.