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

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.