JAK/STAT Signalling in Huntington's Disease Immune Cells

PLoS Curr. 2013 Dec 13:5:ecurrents.hd.5791c897b5c3bebeed93b1d1da0c0648. doi: 10.1371/currents.hd.5791c897b5c3bebeed93b1d1da0c0648.

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene. Both central and peripheral innate immune activation have been described as features of the disease. Isolated human HD monocytes have been shown to produce more cytokines upon LPS stimulation compared to control monocytes. Understanding alterations in the signalling cascades responsible and activated by this increase in pro-inflammatory cytokine production is crucial in understanding the molecular basis of this phenomenon. Here we investigated the signalling cascade most commonly activated by pro-inflammatory cytokines such as IL-6 - the JAK/STAT signalling cascade. Using flow cytometry, we show that one out of three key transcription factors activated by JAK/STAT signalling is altered in primary human HD innate immune cells, suggesting that this pathway may only play a minor, additive role in the immune cell dysfunction in HD.

Grants and funding

This study was funded by UCL/UCLH Biomedical Research Centre (PhD studentship to UT), Medical Research Council, CHDI Foundation, EU FP7 grant (Paddington consortium), the UK Dementia and Neurodegenerative Diseases Network (DeNDRoN) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. EJW is supported by the National Institutes for Health Research and Academy of Medical Sciences.