The Heat Shock Protein HSP70 Promotes Th17 Genes' Expression via Specific Regulation of microRNA

Int J Mol Sci. 2020 Apr 17;21(8):2823. doi: 10.3390/ijms21082823.


T helper cells type 17 (Th17) are orchestrators of autoimmune conditions, including multiple sclerosis (MS), but mechanisms of Th17 pathogenicity remain unknown. MicroRNAs (miRNA) are known to control T cells. To understand the function of miRNA in Th17, we have established a T cell line, EL4-TCR+, that resembles the expression pattern of the Th17 cells. Subsequently, we have evaluated the crosstalk between miRNA and Th17 genes' expression using a combination of gene expression profiling, gene expression manipulation, RNA and protein immunoprecipitation, as well as confocal microscopy. We have found that Th17-related miRNA were strongly expressed in EL4-TCR+ cells following the binding of the cluster of differentiation 3 (CD3) component of the T cell receptor (TCR). Furthermore, a specific inhibition of these miRNA resulted in downregulation of the critical Th17 genes' expression. Surprisingly, this mechanism relied on the function of the stress signal regulator heat shock protein 70 (HSP70). Upon activation, HSP70 co-localized intracellularly with miRNA processing proteins. Precipitation of HSP70 resulted in enrichment of the Th17-associated miRNA. Finally, HSP70 inhibition led to downregulation of the Th17 genes' expression and ameliorated development of autoimmune demyelination. Our study demonstrated that HSP70 facilitates specific miRNA function leading to Th17 genes' expression, a mechanism linking stress and autoimmunity.

Keywords: HSP70; Th17; autoimmune demyelination; experimental autoimmune encephalomyelitis; microRNA; stress response.

MeSH terms

  • Animals
  • CD3 Complex / metabolism*
  • Cell Line
  • Disease Models, Animal
  • Down-Regulation
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Gene Expression Profiling / methods
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Th17 Cells / immunology*


  • CD3 Complex
  • HSP70 Heat-Shock Proteins
  • MicroRNAs