Data from: GDNF-RET signaling drives pulmonary neuroendocrine cell hyperplasia and allergic airway inflammation

Pulmonary neuroendocrine cell (PNEC) hyperplasia often occurs in lung
diseases, including allergic asthma. We previously reported that
PNEC-derived calcitonin gene-related peptide (CGRP) likely stimulates
group 2 innate lymphoid cells (ILC2), exacerbating asthma phenotypes in a
mouse model. Here, we investigate the role of glial cell-line-derived
neurotrophic factor (GDNF) and rearranged during transfection (RET)
signaling in PNEC hyperplasia and its therapeutic potential in asthma.
PNECs expressed GDNF receptors, which were activated primarily by
infiltrating inflammatory cells. Application of a RET-specific inhibitor
suppressed ILC2 levels, PNEC hyperplasia, and airway allergic responses.
We suggest that GDNF-RET signaling promotes PNEC hyperplasia and that the
PNEC-CGRP-ILC2 axis is closely associated with the development of allergic
asthma, presenting a possible new treatment strategy.