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Rapamycin can alleviate the submandibular gland pathology of Sjögren's syndrome by limiting the activation of cGAS–STING signaling pathway

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Abstract

Background

Sjögren’s Syndrome (SS) is also known as autoimmune exocrine gland disease. Previous studies have confirmed that adaptive immunity plays an important role in the development of this disease. But less is known about the role of the innate immune system.

Methods

To identify the core pathways, and local infiltrated immune cells in the local immune microenvironment of SS. We verified the activation of these core genes and core signaling pathways in SS model mice by in vivo experiment and transcriptome sequencing.

Results

Finally, we identified 6 core genes EPSTI1, IFI44L, MX1, CXCL10, IFIT3, and IFI44. All the 6 genes had good diagnostic value. Based on multi-omics sequencing results and experimental studies, we found that cGAS–STING signaling pathway is most relevant to the pathogenesis of SS. By in vivo experiments, we verified that autophagy is the key brake to limit the activation of cGAS–STING signaling pathway.

Conclusions

Maladaptive activation of autophagy and cGAS–STING signaling pathway are central contributors to the SG pathogenesis of pSS patient. Regulating autophagy by rapamycin may be a possible treatment for Sjögren's syndrome in the future.

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Data availability

All the datasets used in the present research are summarized in the Additional file.

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Acknowledgements

We thank the Institute of Pediatrics of Nanjing University of Chinese Medicine for its experimental support and research facility.

Funding

This work was supported by the National Natural Science Foundation of China (grant 82274454) and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX21_1682).

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Author notes

  1. Wen Zhu and Yabei Wang contributed equally to this work.

Authors and Affiliations

  1. Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210032, People’s Republic of China

    Wen Zhu, Yabei Wang, Yin Guan, Yun Lu, Lixia sun & Yue Wang

  2. Gansu Provincial Hospital of Chinese Medicine, Lanzhou, 730000, People’s Republic of China

    Yehui Li

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  1. Wen Zhu
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Contributions

WZ, YBW performed the experiments, conducted the Major data analysis, and finished the original draft. YG, YHL, and YL all wrote the manuscript and prepared figures. LXS and YW designed this study and finished the revision of the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Lixia sun or Yue Wang.

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Zhu, W., Wang, Y., Guan, Y. et al. Rapamycin can alleviate the submandibular gland pathology of Sjögren's syndrome by limiting the activation of cGAS–STING signaling pathway. Inflammopharmacol 32, 1113–1131 (2024). https://doi.org/10.1007/s10787-023-01393-9

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