Final Report Summary - RETIMMUNEFUNCTION (Role of the proto-oncogene Ret during lymphocyte development and function)
Neurotrophic factors are critical molecules for development, survival and function of neurons. Surprisingly we found that neurotrophic factor receptors are expressed by discrete haematopoietic cells, controlling their function and setting haematopoietic activity and immune fitness.
Briefly we found that neurotrophic factor receptor signals provide haematopoietic stem cells (HSC) with critical surviving cues, downstream of p38/MAP kinase and CREB activation. Importantly, activation of neurotrophic factor receptors results in improved HSC survival, expansion and in vivo transplantation efficiency. Remarkably, human cord-blood progenitor expansion and transplantation was also improved by neurotrophic factors, opening the way to explore neurotrophic factor agonists in human HSC transplantation.
Finally, our project showed that unconventional neurotrophic factor receptor responses in trans determine a novel adhesion dependent, chemokine independent triggering phase in enteric lymphoid morphogenesis, thus shedding light on how differential co-expression patterns of neurotrophic factor receptor/co-receptor allow distinct cell lineages to employ identical molecules yet ensuring different outcomes.
Briefly we found that neurotrophic factor receptor signals provide haematopoietic stem cells (HSC) with critical surviving cues, downstream of p38/MAP kinase and CREB activation. Importantly, activation of neurotrophic factor receptors results in improved HSC survival, expansion and in vivo transplantation efficiency. Remarkably, human cord-blood progenitor expansion and transplantation was also improved by neurotrophic factors, opening the way to explore neurotrophic factor agonists in human HSC transplantation.
Finally, our project showed that unconventional neurotrophic factor receptor responses in trans determine a novel adhesion dependent, chemokine independent triggering phase in enteric lymphoid morphogenesis, thus shedding light on how differential co-expression patterns of neurotrophic factor receptor/co-receptor allow distinct cell lineages to employ identical molecules yet ensuring different outcomes.