PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection
| العنوان: | PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection |
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| المؤلفون: | Karthik Mouli, Elena Kamynina, Seth A. Peng, Becca A. Flitter, Bridget M. Mooney, Pamela Campioli, Rebecca L. Cubitt, Michael J. Shanahan, Isabella Rauch, Simon P. Früh, Oyebola O. Oyesola, James D. Lord, Marija S. Nadjsombati, Praveen Sethupathy, Madeline J Churchill, Jakob von Moltke, Shuchi Smita, Karsten Gronert, Macy K. Matheson, Duc H. Pham, Matt Kanke, Jordan L. Cahoon, Elia D. Tait Wojno, Pavithra Sundaravaradan, John W. McGinty, Lauren M. Webb |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, medicine.medical_treatment, Immunology, Innate Immunity and Inflammation, Receptors, Prostaglandin, Inflammation, Article, Host-Parasite Interactions, Infectious Disease and Host Defense, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, parasitic diseases, medicine, Immunology and Allergy, Animals, Nippostrongylus brasiliensis, Intestinal Mucosa, Receptors, Immunologic, Receptor, Strongylida Infections, Goblet cell, biology, Prostaglandin D2, Mucosal Immunology, Hyperplasia, biology.organism_classification, medicine.disease, Epithelium, Cell biology, Gastroenteritis, Mice, Inbred C57BL, Organoids, 030104 developmental biology, medicine.anatomical_structure, Cytokine, chemistry, Cytokines, Female, Goblet Cells, Nippostrongylus, medicine.symptom, 030217 neurology & neurosurgery |
| الوصف: | Type 2 cytokines promote epithelial changes that help to expel worms during intestinal helminth infection. Oyesola et al. show that prostaglandin D2 and its receptor CRTH2 are novel negative regulators of this response, dampening the Type 2 cytokine–mediated program. 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. |
| اللغة: | English |
| تدمد: | 1540-9538 0022-1007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::634e6869920806c0d6f27c6239769b1e http://europepmc.org/articles/PMC8294949 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....634e6869920806c0d6f27c6239769b1e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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