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HDAC3 integrates TGF-β and microbial cues to program tuft cell biogenesis and diurnal rhythms in mucosal immune surveillance.

Authors :
Zhang J
Wang G
Ma J
Duan Y
Sharma SA
Oladejo S
Ma X
Arellano G
Orchard RC
Reese TA
Kuang Z
Source :
Science immunology [Sci Immunol] 2024 Sep 27; Vol. 9 (99), pp. eadk7387. Date of Electronic Publication: 2024 Sep 27.
Publication Year :
2024

Abstract

The intestinal mucosal surface is directly exposed to daily fluctuations in food and microbes driven by 24-hour light and feeding cycles. Intestinal epithelial tuft cells are key sentinels that surveil the gut luminal environment, but how these cells are diurnally programmed remains unknown. Here, we show that histone deacetylase 3 (HDAC3) controls tuft cell specification and the diurnal rhythm of its biogenesis, which is regulated by the gut microbiota and feeding schedule. Disruption of epithelial HDAC3 decreases tuft cell numbers, impairing antihelminth immunity and norovirus infection. Mechanistically, HDAC3 functions noncanonically to activate transforming growth factor-β (TGF-β) signaling, which promotes rhythmic expression of Pou2f3 , a lineage-defining transcription factor of tuft cells. Our findings reveal an environmental-epigenetic link that controls the diurnal differentiation of tuft cells and promotes rhythmic mucosal surveillance and immune responses in anticipation of exogenous challenges.

Details

Language :
English
ISSN :
2470-9468
Volume :
9
Issue :
99
Database :
MEDLINE
Journal :
Science immunology
Publication Type :
Academic Journal
Accession number :
39331726
Full Text :
https://doi.org/10.1126/sciimmunol.adk7387