Format

Send to

Choose Destination
See comment in PubMed Commons below
Nature. 2016 Jan 14;529(7585):226-30. doi: 10.1038/nature16527.

Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites.

Author information

1
CNRS, UMR-5203, Institut de Génomique Fonctionnelle, F-34094 Montpellier, France.
2
INSERM, U1191, F-34094 Montpellier, France.
3
Université de Montpellier, F-34000 Montpellier, France.
4
Institute of Immunology and Infection Research, School of Biological Sciences and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, UK.
5
Monell Chemical Senses Center, 3500 Market Street, Philadelphia, Pennsylvania 19104, USA.
6
Institut de Génétique Moléculaire de Montpellier, CNRS, UMR5535, F-34293 Montpellier, France.

Abstract

Helminth parasitic infections are a major global health and social burden. The host defence against helminths such as Nippostrongylus brasiliensis is orchestrated by type 2 cell-mediated immunity. Induction of type 2 cytokines, including interleukins (IL) IL-4 and IL-13, induce goblet cell hyperplasia with mucus production, ultimately resulting in worm expulsion. However, the mechanisms underlying the initiation of type 2 responses remain incompletely understood. Here we show that tuft cells, a rare epithelial cell type in the steady-state intestinal epithelium, are responsible for initiating type 2 responses to parasites by a cytokine-mediated cellular relay. Tuft cells have a Th2-related gene expression signature and we demonstrate that they undergo a rapid and extensive IL-4Rα-dependent amplification following infection with helminth parasites, owing to direct differentiation of epithelial crypt progenitor cells. We find that the Pou2f3 gene is essential for tuft cell specification. Pou2f3(-/-) mice lack intestinal tuft cells and have defective mucosal type 2 responses to helminth infection; goblet cell hyperplasia is abrogated and worm expulsion is compromised. Notably, IL-4Rα signalling is sufficient to induce expansion of the tuft cell lineage, and ectopic stimulation of this signalling cascade obviates the need for tuft cells in the epithelial cell remodelling of the intestine. Moreover, tuft cells secrete IL-25, thereby regulating type 2 immune responses. Our data reveal a novel function of intestinal epithelial tuft cells and demonstrate a cellular relay required for initiating mucosal type 2 immunity to helminth infection.

PMID:
26762460
DOI:
10.1038/nature16527
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center