PGD2 and CRTH2 Counteract Type 2 Cytokine-elicited Intestinal Epithelial Responses During Helminth Infection

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2021 Jul 20

PMID 34283207

Citations 30

Authors

Oyebola O Oyesola

Michael T Shanahan

Matt Kanke

Bridget M Mooney

Lauren M Webb

Shuchi Smita

Macy K Matheson

Pamela Campioli

Duc Pham

Simon P Fruh

John W McGinty

Madeline J Churchill

Jordan L Cahoon

Pavithra Sundaravaradan

Becca A Flitter

Karthik Mouli

Marija S Nadjsombati

Elena Kamynina

Seth A Peng

Rebecca L Cubitt

Karsten Gronert

James D Lord

Isabella Rauch

Jakob von Moltke

Praveen Sethupathy

Elia D Tait Wojno

Affiliations

Soon will be listed here.

Abstract

Type 2 inflammation is associated with epithelial cell responses, including goblet cell hyperplasia, that promote worm expulsion during intestinal helminth infection. How these epithelial responses are regulated remains incompletely understood. Here, we show that mice deficient in the prostaglandin D2 (PGD2) receptor CRTH2 and mice with CRTH2 deficiency only in nonhematopoietic cells exhibited enhanced worm clearance and intestinal goblet cell hyperplasia following infection with the helminth Nippostrongylus brasiliensis. Small intestinal stem, goblet, and tuft cells expressed CRTH2. CRTH2-deficient small intestinal organoids showed enhanced budding and terminal differentiation to the goblet cell lineage. During helminth infection or in organoids, PGD2 and CRTH2 down-regulated intestinal epithelial Il13ra1 expression and reversed Type 2 cytokine-mediated suppression of epithelial cell proliferation and promotion of goblet cell accumulation. These data show that the PGD2-CRTH2 pathway negatively regulates the Type 2 cytokine-driven epithelial program, revealing a mechanism that can temper the highly inflammatory effects of the anti-helminth response.

Citing Articles

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Tuft cells in the intestine, immunity and beyond.

Feng X, Fluchter P, De Tenorio J, Schneider C Nat Rev Gastroenterol Hepatol. 2024; 21(12):852-868.

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