CCR3 Monoclonal Antibody Inhibits Eosinophilic Inflammation and Mucosal Injury in a Mouse Model of Eosinophilic Gastroenteritis

• Published in: Allergy, asthma & immunology research Vol. 9; no. 4; pp. 360 - 367
• Main Authors: Song, Dae Jin, Shim, Mun Hee, Lee, Nahyun, Yoo, Young, Choung, Ji Tae
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease 01.07.2017; 대한천식알레르기학회
• Subjects: Original; 내과학; eosinophils; CCR3; eosinophilic gastroenteritis
• ISSN: 2092-7355; 2092-7363
• DOI: 10.4168/aair.2017.9.4.360

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. 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. 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. Anti-CCR3 antibody significantly reduced the severity of eosinophilic inflammation, mucosal injury, and diarrhea in a mouse model of food allergen-induced GI eosinophilic inflammation. CCR3 may be a novel therapeutic target for treatment of EGE and other GI eosinophil-mediated diseases.