Protease induced disruption of the epithelial barrier activates a type 2 innate immune lung response. Here we show that activation of the airway epithelium by papain or A. Alternata is regulated by lymphocyte-derived acetylcholine (Ach).
Proteases were administered for three days by intranasal instillation in Ach Transferase (ChAT) reporter, Rag-gc KO and newly created RoRgtCreChATloxp mice. The cell recruitment and inflammatory lung response was analyzed 24h later.
Using ChAT reporter mice, we observe a rapid increase of ACh production by type 2 and 3 innate lymphoid cells (ILC) following papain challenge. To ascertain that the ACh+ILC3 subpopulation contributes to the response, we generated RoRgtCreChATloxp mice. We find decreased eosinophil recruitment, epithelial injury and airway hyperreactivity in ACh+ILC3 deficient mice upon acute papain or A. Alternata challenge.
These findings identify that in addition of ILC2, ILC3-derived ACh as a significant contributor to papain induced allergic asthma.Le texte complet de cet article est disponible en PDF.
Keywords : Asthma, Acetylcholine, Innate lymphoid cells