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The circular RNA circINPP4B acts as a sponge of miR-30a to regulate Th17 cell differentiation during progression of experimental autoimmune encephalomyelitis

Cellular & Molecular Immunology volume 18, pages 2177–2187 (2021)Cite this article

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Abstract

Circular RNAs (circRNAs) regulate gene expression and participate in various biological and pathological processes. However, little is known about the effects of specific circRNAs on T helper cell 17 (Th17) differentiation and related autoimmune diseases, such as multiple sclerosis (MS). Here, using transcriptome microarray analysis at different stages of experimental autoimmune encephalomyelitis (EAE), we identified the EAE progression-related circINPP4B, which showed upregulated expression in Th17 cells from mice with EAE and during Th17 differentiation in vitro. Silencing of circINPP4B inhibited Th17 differentiation and alleviated EAE, characterized by less demyelination and Th17 infiltration in the spinal cord. Mechanistically, circINPP4B served as a sponge that directly targeted miR-30a to regulate Th17 differentiation. Furthermore, circINPP4B levels were associated with the developing phases of clinical relapsing-remitting MS patients. Our results indicate that circINPP4B plays an important role in promoting Th17 differentiation and progression of EAE by targeting miR-30a, which provides a potential diagnostic and therapeutic target for Th17-mediated MS.

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Acknowledgements

We thank the Affiliated Hospital of Xuzhou Medical University for the clinical samples. We thank the Majorbio Cloud Platform for microarray data analysis. This research was supported by the National Natural Science Foundation of China (81771337, 81271345), The National Key R&D Program of China (2017YFA0104202), The Natural Science Foundation of Jiangsu Province (BK20161174), the 333 Project of Jiangsu Province, The Xuzhou Basic Research Science and Technology Project (KC19059) and Xuzhou Medical University Scientific Research Fund for Talents.

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  1. These authors contributed equally: Jingjing Han, Wei Zhuang, Wanhua Feng.

Authors and Affiliations

  1. Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China

    Jingjing Han, Wanhua Feng, Fuxing Dong, Ruiqin Yao & Xuebin Qu

  2. Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China

    Jingjing Han & Fang Hua

  3. Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China

    Wei Zhuang

  4. Institute of Neurological Diseases of Xuzhou Medical University, Xuzhou, Jiangsu, China

    Fang Hua

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Contributions

JJH: designed the research, performed the experiments, analyzed the data, and wrote the paper. WZ: performed the experiments and analyzed the data. WHF: performed the experiments and analyzed the data. FXD: performed the experiments and analyzed the data. FH: designed the research and analyzed the data. RQY: designed the research and analyzed the data. XBQ designed the research, performed the experiments, analyzed the data, and wrote the paper.

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Correspondence to Ruiqin Yao or Xuebin Qu.

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Han, J., Zhuang, W., Feng, W. et al. The circular RNA circINPP4B acts as a sponge of miR-30a to regulate Th17 cell differentiation during progression of experimental autoimmune encephalomyelitis. Cell Mol Immunol 18, 2177–2187 (2021). https://doi.org/10.1038/s41423-021-00748-y

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