Cutting Edge: IL-36 Receptor Promotes Resolution of Intestinal Damage
| Autor: | Hikaru Nishio, Jacob E. Kohlmeier, Ravisankar A. Ramadas, Andrew T. Gewirtz, Asma Nusrat, Benoit Chassaing, Charles A. Parkos, Timothy L. Denning, Duke Geem, Loukia N. Lili, Jennifer E. Towne, Philipp-Alexander Neumann, Oscar Medina-Contreras, Akihito Harusato, Vu L. Ngo, Giovanna Leoni, Kyle L. Flannigan |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Colon Neutrophils Immunology Inflammation Gut flora Inflammatory bowel disease Article 03 medical and health sciences Mice 0302 clinical medicine Intestinal mucosa medicine Immunology and Allergy Animals Humans Colitis Intestinal Mucosa Receptor Mice Knockout Wound Healing biology Interleukins Dextran Sulfate Receptors Interleukin medicine.disease Aryl hydrocarbon receptor biology.organism_classification Inflammatory Bowel Diseases digestive system diseases Mice Inbred C57BL 030104 developmental biology Neutrophil Infiltration Receptors Aryl Hydrocarbon Cancer research biology.protein medicine.symptom Wound healing Helicobacter hepaticus 030215 immunology Interleukin-1 |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 196(1) |
| ISSN: | 1550-6606 |
| Popis: | IL-1 family members are central mediators of host defense. In this article, we show that the novel IL-1 family member IL-36γ was expressed during experimental colitis and human inflammatory bowel disease. Germ-free mice failed to induce IL-36γ in response to dextran sodium sulfate (DSS)-induced damage, suggesting that gut microbiota are involved in its induction. Surprisingly, IL-36R–deficient (Il1rl2−/−) mice exhibited defective recovery following DSS-induced damage and impaired closure of colonic mucosal biopsy wounds, which coincided with impaired neutrophil accumulation in the wound bed. Failure of Il1rl2−/− mice to recover from DSS-induced damage was associated with a profound reduction in IL-22 expression, particularly by colonic neutrophils. Defective recovery of Il1rl2−/− mice could be rescued by an aryl hydrocarbon receptor agonist, which was sufficient to restore IL-22 expression and promote full recovery from DSS-induced damage. These findings implicate the IL-36/IL-36R axis in the resolution of intestinal mucosal wounds. |
| Databáze: | OpenAIRE |
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