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

Area of Science:

• Immunology
• Molecular Biology
• Neuroscience

Background:

• T helper 17 (Th17) cells drive autoimmune diseases like multiple sclerosis (MS).
• Mechanisms of Th17 pathogenicity and the role of microRNAs (miRNAs) in Th17 cells are not fully understood.
• Heat shock protein 70 (HSP70) is a stress regulator with potential roles in immune responses.

Purpose of the Study:

• To elucidate the function of miRNAs in Th17 cells.
• To investigate the role of HSP70 in Th17 cell-mediated autoimmunity.
• To explore the link between cellular stress and autoimmune disease pathogenesis.

Main Methods:

• Established a Th17-like T cell line (EL4-TCR+).
• Utilized gene expression profiling, miRNA inhibition, RNA/protein immunoprecipitation, and confocal microscopy.
• Assessed the impact of HSP70 inhibition on Th17 gene expression and experimental autoimmune demyelination.

Main Results:

• Th17-associated miRNAs were upregulated in activated EL4-TCR+ cells.
• Inhibition of these miRNAs downregulated critical Th17 genes.
• HSP70 co-localized with miRNA processing proteins and facilitated miRNA enrichment, linking HSP70 inhibition to Th17 gene downregulation and ameliorated autoimmune demyelination.

Conclusions:

• HSP70 plays a crucial role in facilitating miRNA function in Th17 cells.
• This HSP70-miRNA axis represents a novel mechanism linking cellular stress to Th17 pathogenicity and autoimmunity.
• Targeting HSP70 may offer a therapeutic strategy for autoimmune demyelinating diseases like MS.