Together, a search for extra-oral channel synapses uncovered sensory end organs for airway protective reflexes in mice, revealing distinct airway defense modalities and their relevance to disease—offering new therapeutic targets.
Check out our paper if you’re interested!—8/9

[Larynx] Finally, we found that laryngeal tuft cells contribute to pathological cough: lower-airway allergen (Alternaria) exposure enhanced T2R ligand (Den)-evoked cough, an effect abolished in Calhm3 KO mice—highlighting a role for tuft cells in allergic hypersensitivity—7/9

[Larynx] Chemical (T2R ligands) and ontogenetic activation of these cells triggered cough-like expulsive reflexes, establishing them as the sensory end organ for the cough reflex to chemical insults—6/9

[Larynx] Single-cell transcriptomics uncovered a subset of tuft cells expressing T2Rs, voltage-gated Na+ channels, and CALHM1/3. In situ voltage and ATP imaging showed they respond to T2R ligand (Denatonium, Den) by firing action potentials and releasing ATP—5/9

[Hypopharynx] Single-cell transcriptomics revealed taste bud cells expressing T2Rs—GPCRs for noxious substances. T2R ligand and ontogenetic activation of them triggered swallowing, establishing them as the sensory end organ for swallowing reflexes to chemical insults—4/9

Whole-body screening revealed two rare epithelial cell populations in the throat that form channel synapses with vagal neurons: type II taste bud cells in the hypopharynx and tuft cells in the larynx—3/9

Channel synapses, first discovered in tongue taste bud cells, release neurotransmitters via CALHM1/3 channel pores—an unconventional, non-vesicular form of synaptic transmission. We hypothesized that a whole-body search could uncover previously unidentified epithelial senses—2/9

The throat initiates airway protective reflexes like swallowing and coughing. Yet, the sensory mechanisms are unclear. Chronic cough affects ~10% globally, with many cases unexplained or refractory, highlighting gaps in our understanding of cough (Nat Rev Dis Primers 8, 45)—1/9

✨New paper from my lab out now in @cp-cell.bsky.social!
We identified pathways for airway protective reflexes—swallowing and coughing—in mice, driven by rare throat chemosensory cells that signal vagal nerves via channel synapses.
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