Unravelling the role of extracellular small heat shock proteins in neuroinflammation

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). During lesion development in MS , there is increased expression of small heat-shock proteins (HSPBs). The protective roles of HSPBs in regulating neural cell survival, inhibiting protein aggregation and regulating inflammation in the CNS is well known. Nonetheless, the extracellular role of HSPBs in neuroinflammation is unclear.

One way that HSPBs are released into the extracellular space is through extracellular vesicles (EV). During neuroinflammation, neural cells (microglia and oligodendrocyte) release EVs either carrying beneficial or detrimental biomarkers into the environment. Here, we characterize the neural cells derived-EV and hypothesize that impaired EV expression can disrupt cell survival communications during neuroinflammation. 

Method: The role of HSPB-EV in inflammation is investigated in 2 steps: 1) Establish HSPBs expressing neural cell lines for the production of HSPB-EV. 2) Isolation and characterization of EV using different techniques. Results: NTA measurement of microglial derived-EV showed an increased EV secretion upon inflammation. Stable HSPBs expressing cell derived-EV revealed a decrease in EV release during inflammation. SPR analysis of oligodendrocyte derived-EV showed interactions with ICAM1 and HSP70. In addition, immunoblot analysis of oligodendrocyte derived-EV showed a downregulation of monomeric HSPB8 and phosphorylated HSPB1 during inflammation.

Summary: Neural cells derived-EVs constitutively express HSPB1 and HSPB8. However upon inflammation, there is a downregulation of both the monomeric forms as well as the phosphorylated HSPB1. This study shows that reduced expression in the extracellular HSPB1/B8-EV upon neuroinflammation can impair neural cell survival signaling. 

Funding: This work was financed by Hasselt University and by EFRO through the Interreg V Grensregio Vlaanderen Nederland project Trans Tech Diagnostics.

Authors

Sam Vanherle (1)
Bram Van den Broek (1)
Vicky De Winter (2)
Revathy Munuswamy (1)
Baharak Hosseinkhani (1)
Vincent Timmerman (2)
Luc Michiels (1)
Joy Irobi (1)

Organisations

Hasselt University, Biomedical research institute (BIOMED), Martelarenlaan 42, 3500 Hasselt, Belgium (1)
Peripheral Neuropathy Group, VIB-Department of Molecular Genetics, University of Antwerp, Antwerpen, Belgium (2)

Presenting author

Joy Irobi, PI, Hasselt University
joy.irobi@uhasselt.be
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