@article{a75a9edaedcf4bafa9014a3abf2015de,
title = "PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection",
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.",
author = "Oyesola, {Oyebola O.} and Shanahan, {Michael T.} and Matt Kanke and Mooney, {Bridget M.} and Webb, {Lauren M.} and Shuchi Smita and Matheson, {Macy K.} and Pamela Campioli and Duc Pham and Fr{\"u}h, {Simon P.} and McGinty, {John W.} and Churchill, {Madeline J.} and Cahoon, {Jordan L.} and Pavithra Sundaravaradan and Flitter, {Becca A.} and Karthik Mouli and Nadjsombati, {Marija S.} and Elena Kamynina and Peng, {Seth A.} and Cubitt, {Rebecca L.} and Karsten Gronert and Lord, {James D.} and Isabella Rauch and {von Moltke}, Jakob and Praveen Sethupathy and {Tait Wojno}, {Elia D.}",
note = "Funding Information: This work was supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (K22 AI116729 and R01 AI130379) to E.D. Tait Wojno; the National Institutes of Health (DP2 0D024087) and the Rainin Foundation Synergy Award to J. von Moltke, I. Rauch, and K. Gronert; the American Diabetes Association Pathway Award (1-16-ACE-47) to P. Sethupathy; Oregon Health and Science University funds to I. Rauch; the National Institutes of Health, National Eye Institute (EY030218 to K. Gronert); and University of Washington startup funds to E.D. Tait Wojno. J. von Moltke is a Searle Scholar. O.O. Oyesola was supported partly by the Cornell African Fellowship and the Cornell Graduate Research Award. J.W. McGinty and M.S. Nadjsombati were supported by the University of Washington Immunology Training Grant T32 AI106677 and M.S. Nadjsombati by the University of Washington Immunology Department Titus Fellowship. Publisher Copyright: {\textcopyright} 2021 Oyesola et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).",
year = "2021",
month = jul,
day = "20",
doi = "10.1084/jem.20202178",
language = "English (US)",
volume = "218",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "9",
}