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Am J Transl Res. 2014 May 15;6(3):312-9. eCollection 2014.

IFN-β alters neurotrophic factor expression in T cells isolated from multiple sclerosis patients - implication of novel neurotensin/NTSR1 pathway in neuroprotection.

Author information

1
University of Colorado School of Medicine Medical Scientist Training Program Aurora, CO, USA.
2
Department of Psychiatry, University of Vermont Burlington, VT, USA.
3
Department of Neurology, Mayo Clinic Rochester, MN, USA.
4
Department of Neurology, Yale University New Haven, CT, USA.
5
Department of Neurology, University of Michigan Ann Arbor, MI, USA.

Abstract

Inflammation in relapsing remitting multiple sclerosis (RRMS) is hypothesized to provide neuroprotective effects via altered cytokine/neurotrophin homeostasis. The distinct neurotrophin production from specific cell populations has not been systematically studied and is likely of high yield in understanding the complex regulation of MS pathogenesis. Here, we describe how the mainstream therapy interferon-β (IFN-β) modulates neurotrophin expression in T cells isolated from RRMS patients and characterize the neuroprotective capabilities of these factors. We utilize SuperArray gene screen technology to investigate the neurotrophin expression profile of T cells. We demonstrate that IFN-β induces an anti-inflammatory cytokine expression pattern in T cells. Additionally, IFN-β upregulates the expression of a novel neurotrophin receptor, the neurotensin high affinity receptor 1 (NTSR1). NTSR1 is expressed in active demyelinating lesions. Furthermore, we demonstrate that the receptor agonist neurotensin is a potent inducer of human neural stem/progenitor cell survival. Our findings highlight the importance of neurotrophin receptors in RRMS and offer insight into disease pathogenesis as well as the mechanisms of action of IFN-β.

KEYWORDS:

Multiple sclerosis; T cells; interferon-beta; neural progenitor cells; neuroprotection; neurotensin high affinity receptor 1

PMID:
24936223
PMCID:
PMC4058312
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