Engaging the immune system for remyelination in the brain using BDNF-engineered regulatory T cells.

Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS), characterized by inflammatory attacks against the myelin sheath. Today, over 10 disease-modifying therapies are approved, predominantly focusing on immunomodulation. However, remyelination remains a major unmet clinical need in (progressive) MS therapy. Today, efforts are made to unravel de- and remyelinating mechanisms. Therefore, brain-derived neurotrophic factor (BDNF) seems an interesting protein, as it promotes neuroprotection and (re)myelination. Interestingly, BDNF levels are reported to be reduced in MS. While neurons are the principal source of BDNF in the CNS, key-immune cells can also secrete BDNF, suggesting that BDNF mediates the cross-talk between the immune- and nervous system. Recently, a growing body of research underscoring the key role of regulatory T cells (Treg) in MS, has emerged. Interestingly, a novel pro-regenerative function of Treg was revealed, mediated by the secretion of pro-myelinating factors. Nevertheless, the relation between immune cell-mediated BDNF expression and its accompanying effects in the CNS, such as remyelination, remains elusive in MS. Therefore, we aim to investigate the influence of immune cell-induced BDNF expression on remyelination using state-of-the-art techniques and patient samples. Our findings may result in the development of novel strategies to improve remyelination, predominantly focussing on progressive MS treatment.

Keywords:REGENERATION CAPACITY

Disciplines:Applied immunology, Autoimmunity, Neurological and neuromuscular diseases