Mast cell-derived neurotrophin 4 mediates allergen-induced airway hyperinnervation in early life.

ABSTRACT: Asthma often progresses from early episodes of insults. How early-life events connect to long-term airway dysfunction remains poorly understood. We demonstrated previously that increased neurotrophin 4 (NT4) levels following early-life allergen exposure cause persistent changes in airway smooth muscle (ASM) innervation and airway hyper-reactivity (AHR) in mice. Herein, we identify pulmonary mast cells as a key source of aberrant NT4 expression following early insults. NT4 is selectively expressed by ASM and mast cells in mice, nonhuman primates, and humans. We show in mice that mast cell-derived NT4 is dispensable for ASM innervation during development. However, upon insults, mast cells expand in number and degranulate to release NT4 and thus become the major source of NT4 under pathologic

SUBMITTER: Patel KR 

PROVIDER: S-EPMC4980297 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature