Neuro-immune interactions in chemical-induced airway hyperreactivity

Eur Respir J. 2016 Aug;48(2):380-92. doi: 10.1183/13993003.01778-2015. Epub 2016 Apr 28.


Asthma may be induced by chemical sensitisers, via mechanisms that are still poorly understood. This type of asthma is characterised by airway hyperreactivity (AHR) and little airway inflammation. Since potent chemical sensitisers, such as toluene-2,4-diisocyanate (TDI), are also sensory irritants, it is suggested that chemical-induced asthma relies on neuro-immune mechanisms.We investigated the involvement of transient receptor potential channels (TRP) A1 and V1, major chemosensors in the airways, and mast cells, known for their ability to communicate with sensory nerves, in chemical-induced AHR.In vitro intracellular calcium imaging and patch-clamp recordings in TRPA1- and TRPV1-expressing Chinese hamster ovarian cells showed that TDI activates murine TRPA1, but not TRPV1. Using an in vivo model, in which an airway challenge with TDI induces AHR in TDI-sensitised C57Bl/6 mice, we demonstrated that AHR does not develop, despite successful sensitisation, in Trpa1 and Trpv1 knockout mice, and wild-type mice pretreated with a TRPA1 blocker or a substance P receptor antagonist. TDI-induced AHR was also abolished in mast cell deficient Kit(Wsh) (/Wsh) mice, and in wild-type mice pretreated with the mast cell stabiliser ketotifen, without changes in immunological parameters.These data demonstrate that TRPA1, TRPV1 and mast cells play an indispensable role in the development of TDI-elicited AHR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / immunology*
  • Bronchial Hyperreactivity / immunology*
  • CHO Cells
  • Calcium / metabolism
  • Cricetulus
  • Inflammation
  • Mast Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Neurological
  • Patch-Clamp Techniques
  • Sensory Receptor Cells / immunology
  • TRPA1 Cation Channel / metabolism*
  • TRPV Cation Channels / metabolism*
  • Toluene 2,4-Diisocyanate / chemistry


  • TRPA1 Cation Channel
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Trpa1 protein, mouse
  • Toluene 2,4-Diisocyanate
  • Calcium