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PSMC6 induces immune cell infiltration and inflammatory response to aggravate primary Sjögren’s syndrome

Journal of Human Genetics volume 68, pages 263–271 (2023)Cite this article

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Abstract

Increasing evidence suggests that immune cell infiltration is involved in primary Sjögren’s syndrome (pSS), while the underlying molecular mechanisms remain elusive. Herein, this study aims to explore the key molecular mechanism in immune cell infiltration in pSS based on Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained, followed by weighted gene co-expression network analysis to acquire the pSS-related module genes. Moreover, pSS-related DEGs and module genes were intersected. Additionally, the correlation between key genes and immune cell infiltration was analyzed by CIBERSORT algorithm. Furthermore, pSS mouse models were established to explore the effects of PSMC6 on immune cell infiltration and inflammatory responses in pSS. A total of 51 DEGs and 334 key module genes were involved in the occurrence of pSS. The immune cell infiltration was correlated with pSS, and PSMC6, highly expressed in pSS samples, may be the key immune gene. In vivo animal experiments demonstrated that PSMC6 was upregulated in pSS, and PSMC6 knockdown could reduce lymphocytic infiltration in salivary glands and lacrimal glands and the levels of related inflammatory factors in the pSS and increase the proportion of Treg cells. Collectively, PSMC6 could induce immune cell infiltration and inflammatory responses to promote the occurrence of pSS, providing us with a potential therapeutic target for treating pSS.

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Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

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Funding

This study was funded by Chunhui Program of the Ministry of Education (z2010041), Natural Science Foundation of Heilongjiang Province (H2017064) and Project of Heilongjiang Traditional Chinese Medicine Association (21102190004).

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Author notes

  1. These authors contributed equally: Yongzhu Piao, Yutong Qi.

Authors and Affiliations

  1. Department of Rheumatology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, 150040, P. R. China

    Yongzhu Piao & Hao Zhang

  2. Department of Rheumatology and Immunology, Yancheng Chinese Medicine Hospital, Yancheng, 224000, P. R. China

    Yutong Qi

  3. Department of Preventive Medicine, Beijing Longfu Hospital, Beijing, 100010, P. R. China

    Longyin Han

  4. Heilongjiang University of Chinese Medicine, Harbin, 150040, P. R. China

    Xiayuan Zhong & Qingnan Liu

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  1. Yongzhu Piao
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  4. Longyin Han
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  6. Qingnan Liu
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Contributions

Conceived and designed the experiments: YZP, YTQ. Performed experimental: HZ, LYH. Performed experimental validation: XYZ, QNL. Analyzed the data and conceived figures and tables: XYZ, QNL. Wrote the paper: YZP, YTQ. Contributed to the writing of the manuscript: HZ, LYH. All authors revised and approved the final version of the manuscript.

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Correspondence to Yongzhu Piao.

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Piao, Y., Qi, Y., Zhang, H. et al. PSMC6 induces immune cell infiltration and inflammatory response to aggravate primary Sjögren’s syndrome. J Hum Genet 68, 263–271 (2023). https://doi.org/10.1038/s10038-022-01107-z

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