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MiR-30a-centered molecular crosstalk regulates Th17 differentiation

Cellular & Molecular Immunology volume 19, pages 960–961 (2022)Cite this article

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Recently, there has been growing interest in the specific role of Th17 cells in the pathogenesis of neuroinflammation-related degenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) [1]. The Th17-mediated autoimmune response is a key determinant of these pathological outcomes. Interleukin-17 (IL-17), the most important cytokine of activated Th17 cells, is considered a pivotal agent of autoimmunity because of its proinflammatory effect and migration-promoting ability. Although the specific mechanism of Th17/IL-17 is still controversial, exploring the molecular pathways of Th17/IL-17 in neurodegeneration will facilitate the identification of suitable targets to modulate these cellular processes. Th17 differentiation is directed by lineage-specific transcription factors, including RORγt and RORα, and is controlled by the coordinated activity of a series of positive and negative regulators, as well as additional signals from different cytokines to maintain and stabilize the proinflammatory features of Th17 cells [2, 3]. An accumulating body of research indicates that the potential regulation of Th17 differentiation to maintain the balance of the immune microenvironment is an effective strategy for the prevention and treatment of neurological autoimmune diseases. A recent study published in Cellular & Molecular Immunology demonstrated that the circINPP4B/miR-30a/IL-21R axis plays a key role in promoting Th17 differentiation and experimental autoimmune encephalomyelitis (EAE) progression [4], providing a potential diagnostic and therapeutic target for Th17-mediated MS disease.

MiRNA dysregulation may arise due to various factors, such as epigenetic modifications, transcription factors (TFs) and processing proteins, at each stage during their transcriptional and posttranscriptional biogenesis. Promoter-associated CpG island methylation is a major epigenetic mechanism underlying miRNA regulation, and approximately 50% of miRNA genes are associated with CpG islands. Unfortunately, using bioinformatics tools, we did not find CpG island regions in the promoter of Mir-30a. In the cytoplasm, there is a kind of special competing endogenous RNA, circular RNA (circRNA), which is defined as a miRNA sponge that binds miRNAs and thus prevents them from binding and suppressing their target mRNAs [11]. An increasing number of studies have confirmed that circRNAs participate in the progression of neurodegenerative disorders and autoimmune diseases by regulating cell proliferation, differentiation, apoptosis, invasion, and metastasis. To explore the specific circRNAs mediating Th17 differentiation and EAE progression, we analyzed all the differential expression of circRNAs in serum from mice at different pathological stages of EAE by transcriptome microarray and identified the EAE progression-related circINPP4B, which served as a sponge that directly targeted miR-30a to regulate Th17 differentiation [4] (Fig. 1). Moreover, clinical trials have shown that circINPP4B levels are associated with the characteristics of MS, serving as a potential novel biomarker for diagnosis.

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Acknowledgements

We thank Figdraw (www.figdraw.com) for providing scientific drawing materials. This work was supported by the National Natural Science Foundation of China (81302519), Natural Science Foundation of Jiangsu Province (BK20130221), 333 Project of Jiangsu Province, Scientific Research Funds of Xuzhou Medical University and Jiangsu Vocational College of Medicine.

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  1. Department of Basic Medical Science, Jiangsu Vocational College of Medicine, Yancheng, 224008, Jiangsu, China

    Jingjing Han, Liucai Yang & Xuebin Qu

  2. Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China

    Jingjing Han

  3. Department of Cell Biology and Neurobiology, Xuzhou Medical University, Xuzhou, 221009, Jiangsu, China

    Wanhua Feng, Ruiqin Yao & Xuebin Qu

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Correspondence to Liucai Yang or Xuebin Qu.

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Han, J., Feng, W., Yao, R. et al. MiR-30a-centered molecular crosstalk regulates Th17 differentiation. Cell Mol Immunol 19, 960–961 (2022). https://doi.org/10.1038/s41423-022-00888-9

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