CCR3 monoclonal antibody inhibits eosinophilic inflammation and mucosal injury in a mouse model of eosinophilic gastroenteritis

Dae Jin Song, Mun Hee Shim, Nahyun Lee, Young Yoo, Ji Tae Choung

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Although the role of eosinophils in eosinophilic gastroenteritis (EGE) is not fully understood, they are believed to be a principal effector cell. Previous studies have demonstrated that eotaxin and its specific receptor, cysteine-cysteine chemokine receptor-3 (CCR3), play a central role in eosinophil trafficking into the gastrointestinal (GI) tract. Thus, we examined the targeting of CCR3 as a potential therapeutic intervention for EGE in a mouse model. Methods: Eight- to 10-week-old BALB/c mice were intraperitoneally sensitized and intragastrically challenged with ovalbumin (OVA). Different groups of mice were administered either an anti-CCR3 antibody or a control IgG by intraperitoneal injection 1 hour before each OVA challenge. Eosinophilic inflammation in the intestinal mucosa, mucosal injury, and severity of diarrhea were compared between different groups at 1 hour after final OVA challenge. Results: Anti-CCR3 antibody reduced the number of eosinophils in peripheral blood and intestinal mucosa, but not in bone marrow. This reduction was associated with restoration of reduced villous crypt ratio, increased intestinal epithelial cell proliferation, and weight loss induced by OVA challenge. However, Anti-CCR3 antibody had no effect on the level of OVA specific immunoglobulin E (IgE) and the expression of critical chemokines or cytokines in eosinophil trafficking into the GI tract, such as eotaxin-1, interleukin (IL)-5, and IL-13. Conclusions: Anti-CCR3 antibody significantly reduced the severity of eosinophilic inflammation, mucosal injury, and diarrhea in a mouse model of food allergeninduced GI eosinophilic inflammation. CCR3 may be a novel therapeutic target for treatment of EGE and other GI eosinophil-mediated diseases.

Original languageEnglish
Pages (from-to)360-367
Number of pages8
JournalAllergy, Asthma and Immunology Research
Volume9
Issue number4
DOIs
Publication statusPublished - 2017

Keywords

  • CCR3
  • Eosinophilic gastroenteritis
  • Eosinophils

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine

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