Gerbe, F. et al. (2016) Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature, 529(7585), pp. 226-230. (doi: 10.1038/nature16527) (PMID:26762460)
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Abstract
Helminth parasitic infections are a major global health and social burden1. The host defence against helminths such as Nippostrongylus brasiliensis is orchestrated by type 2 cell-mediated immunity2. Induction of type 2 cytokines, including interleukins (IL) IL-4 and IL-13, induce goblet cell hyperplasia with mucus production, ultimately resulting in worm expulsion3, 4. 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 epithelium5, are responsible for initiating type 2 responses to parasites by a cytokine-mediated cellular relay. Tuft cells have a Th2-related gene expression signature6 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.
| Item Type: | Articles |
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| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Maizels, Professor Rick and Smyth, Dr Danielle |
| Authors: | Gerbe, F., Sidot, E., Smyth, D. J., Ohmoto, M., Matsumoto, I., Dardalhon, V., Cesses, P., Garnier, L., Pouzolles, M., Brulin, B., Bruschi, M., Harcus, Y., Zimmermann, V. S., Taylor, N., Maizels, R. M., and Jay, P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Nature |
| Publisher: | Nature Publishing Group |
| ISSN: | 0028-0836 |
| ISSN (Online): | 1476-4687 |
| Published Online: | 13 January 2016 |
| Copyright Holders: | Copyright © 2016 Macmillan Publishers Limited |
| First Published: | First published in Nature 529(7585): 226-230 |
| Publisher Policy: | Reproduced in accordance with the publisher copyright policy |
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