Journal of Transmitted Diseases and Immunity

Neuronal IFN-beta - induced PI3K/Akt-FoxA1 signaling is essential for generation of FoxA1+Treg cells

Joint Event on 22^nd Edition of International Conference on Immunology and Evolution of Infectious Diseases & 12^th Edition of International Conference on Tissue Engineering and Regenerative Medicine
May 10-11, 2018 Frankfurt, Germany

Yawei Liu, Andrea Marin, Patrick Ejlerskov, Louise Munk Rasmussen, Marco Prinz and Shohreh Issazadeh-Navikas

BRIC - University of Copenhagen, Denmark Institute for Neuropathology - University of Copenhagen, Germany Centre for Biological Signaling Studies - University of Copenhagen, Germany

Posters & Accepted Abstracts: J Transm Dis Immun

DOI: 10.21767/2573-0320-C2-006

Abstract

Neurons reprogram encephalitogenic T cells (T(enc)) to become regulatory Treg cells FoxP3+Tregs or FoxA1+Tregs. We reported previously that neuronal ability to generate FoxA1+Tregs was central to preventing neuroinflammation in experimental autoimmune encephalomyelitis (EAE). Mice lacking the cytokine interferon (IFN)�?² were defective in generating FoxA1+Tregs in the brain. Neuron-induced FoxA1+Tregs were capable of preventing chronic and demyelinating EAE in mice lacking IFN�?²ï¢. Here we show that lack of neuronal IFN�?²ï¢signaling was associated with lack of neuronal expression of program death-ligand1 (PDL1), which also prevented their ability to reprogram Tenc cells to FoxA1+Tregs. Transfer of IFN�?²ï¢ competent encephalitogenic T cells to mice lacking IFN�?²ï¢ or its receptor; IFN AR in the brain (NesCre:Ifnarfl/fl) led to the absence of FoxA1+Tregs generation and aggravated neuroinflammation. We identified that IFN�?²ï¢ activated neuronal PI3K/Akt signaling. Phosphorylated Akt consequently bound to transcription factor FoxA1, which upon translocation to the nucleus induced neuronal PDL1 expression. Conversely, inhibition of PI3K/Akt, or FoxA1 and PDL1 knock-down blocked neuronal ability to generate FoxA1+Tregs. Our study identified crucial molecular playerâ�?�?s central for neuronal ability to reprogram pathogenic T-cells and to generate FoxA1+Tregs, which could be a therapeutic target to prevent neuroinflammation.

Biography

Yawei Liu has a medical doctor background and has been doing medical research for more than 10 years. Since her Ph.D., she mainly focused on the role of neurons in the regulation of auto-reactive T cells and central nervous system (CNS) inflammation. We reported a novel function for neurons as being highly immune-competent cells, based on their crucial role in the regulation of T-cell responses and CNS inflammation in models of multiple sclerosis

Email:Yawei.liu@bric.ku.dk