Tuft cell IL-17RB restrains IL-25 bioavailability and reveals context-dependent ILC2 hypoproliferation.
bioRxiv
; 2024 Mar 08.
Article
in En
| MEDLINE
| ID: mdl-38496438
ABSTRACT
The tuft cell-ILC2 circuit orchestrates rapid type 2 responses upon detecting microbe-derived succinate and luminal helminths. Our findings delineate key mechanistic steps, involving IP3R2 engagement and Ca 2+ flux, governing IL-25 production by tuft cells triggered by succinate detection. While IL-17RB plays a pivotal intrinsic role in ILC2 activation, it exerts a regulatory function in tuft cells. Tuft cells exhibit constitutive Il25 expression, placing them in an anticipatory state that facilitates rapid production of IL-25 protein for ILC2 activation. Tuft cell IL-17RB is crucial for restraining IL-25 bioavailability, preventing excessive tonic ILC2 stimulation due to basal Il25 expression. Suboptimal ILC2 stimulation by IL-25 resulting from tuft cell Il17rb -deficiency or prolonged succinate exposure induces a state of hypoproliferation in ILC2s, also observed in chronic helminth infection. Our study offers critical insights into the regulatory dynamics of IL-25 in this circuit, highlighting the delicate tuning required for responses to diverse luminal states.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
BioRxiv
Year:
2024
Document type:
Article