Desaminotyrosine promotes tuft cell expansion and integrates intestinal type 2 immunity

TL;DR

A small molecule called desaminotyrosine helps protect against parasites by boosting specific immune cells in the gut.

Contribution

This study reveals a new role for desaminotyrosine in anti-parasitic immunity through tuft cell expansion and HDAC3-dependent mechanisms.

Findings

Desaminotyrosine promotes tuft cell hyperplasia and type 2 immunity in the small intestine.

DAT's effects on tuft cells and immunity depend on HDAC3 and a healthy microbiota.

DAT fine-tunes intestinal defenses against helminth infections.

Abstract

Intestinal microbiota are essential for maintaining the host’s immune homeostasis, but the mechanism is not fully understood. While microbial metabolite desaminotyrosine (DAT) is recognized for its protective role in viral immunity, its potential involvement in anti-parasitic defense remains unexplored. Here, we demonstrate that DAT orchestrates tuft cell hyperplasia and subsequent type 2 immunity, establishing critical defense against helminth infection. Mechanistically, DAT-mediated intestinal epithelial remodeling requires histone deacetylase 3 (HDAC3), as pharmacological inhibition of this epigenetic regulator abrogates both tuft cell expansion and impairs type 2 immune responses. Collectively, our findings not only explore DAT novel effects in anti-parasitic defense but also reveal a pathway whereby the small molecule metabolites calibrate intestinal type 2 immunity.

A small molecule metabolite DAT drives tuft cell hyperplasia and type 2 immunity in the small intestine. DAT-mediated tuft cell hyperplasia depends on HDAC3 and an intact microbiota; our findings reveal how small molecule metabolites fine-tune intestinal type 2 defenses against parasites.

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