دورية أكاديمية

PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection

التفاصيل البيبلوغرافية
العنوان: PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection
المؤلفون: Oyesola, Oyebola O., Shanahan, Michael T., Kanke, Matt, Mooney, Bridget M., Webb, Lauren M., Smita, Shuchi, Matheson, Macy K., Campioli, Pamela, Pham, Duc, Früh, Simon P., McGinty, John W., Churchill, Madeline J., Cahoon, Jordan L., Sundaravaradan, Pavithra, Flitter, Becca A., Mouli, Karthik, Nadjsombati, Marija S., Kamynina, Elena, Peng, Seth A., Cubitt, Rebecca L., Gronert, Karsten, Lord, James D., Rauch, Isabella, von Moltke, Jakob, Sethupathy, Praveen, Tait Wojno, Elia D.
المساهمون: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Rainin Foundation, American Diabetes Association, Oregon Health and Science University, National Eye Institute, University of Washington
المصدر: Journal of Experimental Medicine ; volume 218, issue 9 ; ISSN 0022-1007 1540-9538
بيانات النشر: Rockefeller University Press
سنة النشر: 2021
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1084/jem.20202178
DOI: 10.1084/jem.20202178/1775620/jem_20202178.pdf
الإتاحة: https://doi.org/10.1084/jem.20202178Test
حقوق: https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.95A4BBC8
قاعدة البيانات: BASE