CCR8 leads to eosinophil migration and regulates neutrophil migration in murine allergic enteritis
- Allergic enteritis (AE) is a gastrointestinal form of food allergy. This study aimed to elucidate cellular and molecular mechanisms of AE using a murine model. To induce AE, BALB/c wild type (WT) mice received intraperitoneal sensitization with ovalbumin (an egg white allergen) plus ALUM and feeding an egg white (EW) diet. Microarray analysis showed enhanced gene expression of CC chemokine receptor (CCR) 8 and its ligand, chemokine CC motif ligand (CCL) 1 in the inflamed jejunum. Histological and FACS analysis showed that CCR8 knock out (KO) mice exhibited slightly less inflammatory features, reduced eosinophil accumulation but accelerated neutrophil accumulation in the jejunums, when compared to WT mice. The concentrations of an eosinophil chemoattractant CCL11 (eotaxin-1), but not of IL-5, were reduced in intestinal homogenates of CCR8KO mice, suggesting an indirect involvement of CCR8 in eosinophil accumulation in AE sites by inducing CCL11 expression. The potential of CCR8 antagonists to treat allergic asthma has been discussed. However, our results suggest that CCR8 blockade may promote neutrophil accumulation in the inflamed intestinal tissues, and not be a suitable therapeutic target for AE, despite the potential to reduce eosinophil accumulation. This study advances our knowledge to establish effective anti-inflammatory strategies in AE treatment.
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| Author: | Frank Eliezer Blanco PérezORCiDGND, Yoichiro Kato, Irene Gonzalez-MenendezGND, Jonathan LaiñoORCiD, Masaharu Ohbayashi, Manja Burggraf, Maren Krause, Jörg Kirberg, Yoichiro IwakuraORCiD, Manuela Martella, Leticia Quintanilla-MartinezORCiDGND, Noriyuki Shibata, Stefan ViethsGND, Stephan ScheurerORCiD, Masako Toda |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-525560 |
| DOI: | https://doi.org/10.1038/s41598-019-45653-7 |
| ISSN: | 2045-2322 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31270368 |
| Parent Title (English): | Scientific reports |
| Publisher: | Macmillan Publishers Limited, part of Springer Nature |
| Place of publication: | [London] |
| Document Type: | Article |
| Language: | English |
| Year of Completion: | 2019 |
| Date of first Publication: | 2019/07/03 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2020/01/27 |
| Tag: | Acute inflammation; Inflammation |
| Volume: | 9 |
| Issue: | 1, Art. 9608 |
| Page Number: | 13 |
| First Page: | 1 |
| Last Page: | 13 |
| Note: | Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| HeBIS-PPN: | 45985741X |
| Institutes: | Medizin / Medizin |
| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - Namensnennung 4.0 |
