PGD2 and CRTH2 counteract Type 2 cytokine-elicited intestinal epithelial responses during helminth infection.
Animals
Cytokines
/ metabolism
Female
Gastroenteritis
/ parasitology
Goblet Cells
/ pathology
Host-Parasite Interactions
/ physiology
Intestinal Mucosa
/ parasitology
Male
Mice, Inbred C57BL
Nippostrongylus
/ pathogenicity
Organoids
Prostaglandin D2
/ metabolism
Receptors, Immunologic
/ genetics
Receptors, Prostaglandin
/ genetics
Strongylida Infections
/ parasitology
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
06 09 2021
06 09 2021
Historique:
received:
10
10
2020
revised:
28
04
2021
accepted:
21
06
2021
entrez:
20
7
2021
pubmed:
21
7
2021
medline:
25
11
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34283207
pii: 212485
doi: 10.1084/jem.20202178
pmc: PMC8294949
pii:
doi:
Substances chimiques
Cytokines
0
Receptors, Immunologic
0
Receptors, Prostaglandin
0
Prostaglandin D2
RXY07S6CZ2
prostaglandin D2 receptor
XZF106QU24
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : DP2 AI136596
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI106677
Pays : United States
Organisme : NIH HHS
ID : S10 OD024979
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY026082
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY030218
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145848
Pays : United States
Organisme : NIH HHS
ID : DP2 0D024087
Pays : United States
Organisme : NIAID NIH HHS
ID : K22 AI116729
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI130379
Pays : United States
Organisme : NEI NIH HHS
ID : EY030218
Pays : United States
Informations de copyright
© 2021 Oyesola et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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