Increasing evidence supports the idea that the nervous system communicates with and influences responses of the immune system. In Nature, Fonseca-Pereira et al. show that hematopoietic stem cells (HSCs) express the tyrosine receptor kinase RET, which signals in response to neurotrophic factors of the GDNF family. HSCs lacking RET have diminished fitness and are unable to reconstitute hematopoiesis in irradiated recipients. GDNF-RET signaling induces expression of the prosurvival molecules Bcl-2 and Bcl-2L1 dependent on the mitogen-activated protein kinase p38. Overexpression of either molecule can 'rescue' RET deficiency in HSCs. Moreover, treatment of wild-type HSCs with GDNF improves their transplantation efficiency, probably by enhancing their survival. These findings suggest that neuronal communication within the bone marrow stem cell niche might contribute the regulation of HSC fitness and response to physiological stress.

Nature 514, 98–101 (2014)