CCR8 leads to eosinophil migration and regulates neutrophil migration in murine allergic enteritis

• Autores: Blanco Pérez, Frank; Kato, Yoichiro; Gonzalez Menendez, Irene; Laiño, Jonathan Emiliano; Ohbayashi, Masaharu; Burggraf, Manja; Krause, Maren; Kirberg, Jörg; Iwakura, Yoichiro; Martella, Manuela; Quintanilla Martinez, Leticia; Shibata, Noriyuki; Vieths, Stefan; Scheurer, Stephan; Toda, Masako
• Año de publicación: 2019
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: ACUTE INFLAMMATION; INFLAMMATION; ALLERGIC ENTERITIS; FOOD ALLERGY
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Blanco-Pérez, Frank. Paul-ehrlich-institut;
Fil: Kato, Yoichiro. Tokyo Women's Medical University;
Fil: Gonzalez-Menendez, Irene. Universitätsklinikum Tübingen Medizinische Fakultät;
Fil: Laiño, Jonathan Emiliano. Paul-ehrlich-institut;
Fil: Ohbayashi, Masaharu. Toyohashi Sozo University;
Fil: Burggraf, Manja. Paul-ehrlich-institut;
Fil: Krause, Maren. Paul-ehrlich-institut;
Fil: Kirberg, Jörg. Paul-ehrlich-institut;
Fil: Iwakura, Yoichiro. Tokyo University Of Science;
Fil: Martella, Manuela. Universitätsklinikum Tübingen Medizinische Fakultät;
Fil: Quintanilla-Martinez, Leticia. Universitätsklinikum Tübingen Medizinische Fakultät;
Fil: Shibata, Noriyuki. Tokyo Women's Medical University;
Fil: Vieths, Stefan. Paul-ehrlich-institut;
Fil: Scheurer, Stephan. Paul-ehrlich-institut;
Fil: Toda, Masako. Paul-ehrlich-institut; . Tohoku University;