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PGD2 and CRTH2 counteract Type 2 cytokine-elicited intestinal epithelial responses during helminth infection.
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.
Affiliation
  • Oyesola OO; Department of Immunology, University of Washington, Seattle, WA.
  • Shanahan MT; Baker Institute for Animal Health and Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY.
  • Kanke M; Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY.
  • Mooney BM; Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY.
  • Webb LM; Department of Immunology, University of Washington, Seattle, WA.
  • Smita S; Department of Immunology, University of Washington, Seattle, WA.
  • Matheson MK; Department of Immunology, University of Washington, Seattle, WA.
  • Campioli P; Department of Immunology, University of Washington, Seattle, WA.
  • Pham D; Baker Institute for Animal Health and Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY.
  • Früh SP; Baker Institute for Animal Health and Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY.
  • McGinty JW; Baker Institute for Animal Health and Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY.
  • Churchill MJ; Department of Immunology, University of Washington, Seattle, WA.
  • Cahoon JL; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR.
  • Sundaravaradan P; Department of Immunology, University of Washington, Seattle, WA.
  • Flitter BA; Department of Immunology, University of Washington, Seattle, WA.
  • Mouli K; Vision Science Program, School of Optometry, University of California, Berkeley, Berkeley, CA.
  • Nadjsombati MS; Vision Science Program, School of Optometry, University of California, Berkeley, Berkeley, CA.
  • Kamynina E; Department of Immunology, University of Washington, Seattle, WA.
  • Peng SA; Baker Institute for Animal Health and Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY.
  • Cubitt RL; Baker Institute for Animal Health and Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY.
  • Gronert K; Baker Institute for Animal Health and Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY.
  • Lord JD; Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY.
  • Rauch I; Vision Science Program, School of Optometry, University of California, Berkeley, Berkeley, CA.
  • von Moltke J; Benaroya Research Institute at Virginia Mason Medical Center, Division of Gastroenterology, Seattle, WA.
  • Sethupathy P; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR.
  • Tait Wojno ED; Department of Immunology, University of Washington, Seattle, WA.
J Exp Med ; 218(9)2021 09 06.
Article in En | MEDLINE | ID: mdl-34283207
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.
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Full text: 1 Database: MEDLINE Main subject: Receptors, Prostaglandin / Receptors, Immunologic / Prostaglandin D2 / Cytokines / Strongylida Infections / Intestinal Mucosa Limits: Animals Language: En Year: 2021 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Receptors, Prostaglandin / Receptors, Immunologic / Prostaglandin D2 / Cytokines / Strongylida Infections / Intestinal Mucosa Limits: Animals Language: En Year: 2021 Type: Article