Nasal solitary chemosensory cells govern daily rhythm in mouse model of allergic rhinitis.
J Allergy Clin Immunol
; 154(3): 707-718, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38734385
ABSTRACT
BACKGROUND:
While the daily rhythm of allergic rhinitis (AR) has long been recognized, the molecular mechanism underlying this phenomenon remains enigmatic.OBJECTIVE:
We aimed to investigate the role of circadian clock in AR development and to clarify the mechanism by which the daily rhythm of AR is generated.METHODS:
AR was induced in mice with ovalbumin. Toluidine blue staining, liquid chromatography-tandem mass spectrometry analysis, real-time quantitative PCR, and immunoblotting were performed with AR and control mice.RESULTS:
Ovalbumin-induced AR is diurnally rhythmic and associated with clock gene disruption in nasal mucosa. In particular, Rev-erbα is generally downregulated and its rhythm retained, but with a near-12-hour phase shift. Furthermore, global knockout of core clock gene Bmal1 or Rev-erbα increases the susceptibility of mice to AR and blunts AR rhythmicity. Importantly, nasal solitary chemosensory cells (SCCs) are rhythmically activated, and inhibition of the SCC pathway leads to attenuated AR and a loss of its rhythm. Moreover, rhythmic activation of SCCs is accounted for by diurnal expression of ChAT (an enzyme responsible for the synthesis of acetylcholine) and temporal generation of the neurotransmitter acetylcholine. Mechanistically, Rev-erbα trans-represses Chat through direct binding to a specific response element, generating a diurnal oscillation in this target gene.CONCLUSION:
SCCs, under the control of Rev-erbα, are a driver of AR rhythmicity; targeting SCCs should be considered as a new avenue for AR management.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Circadian Rhythm
/
Disease Models, Animal
/
Rhinitis, Allergic
/
Nasal Mucosa
Limits:
Animals
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United States