1. CCR4 Is Critically Involved in Skin Allergic Inflammation of BALB/c Mice.
- Author
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Matsuo K, Nagakubo D, Komori Y, Fujisato S, Takeda N, Kitamatsu M, Nishiwaki K, Quan YS, Kamiyama F, Oiso N, Kawada A, Yoshie O, and Nakayama T
- Subjects
- Animals, Bacterial Toxins administration & dosage, Bacterial Toxins immunology, Dermatitis, Atopic pathology, Disease Models, Animal, Eosinophils immunology, Humans, Mast Cells immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Ovalbumin administration & dosage, Ovalbumin immunology, Receptors, CCR4 antagonists & inhibitors, Receptors, CCR4 genetics, Receptors, CCR4 metabolism, Skin cytology, Skin immunology, Skin pathology, Th17 Cells metabolism, Th2 Cells metabolism, Dermatitis, Atopic immunology, Receptors, CCR4 immunology, Th17 Cells immunology, Th2 Cells immunology
- Abstract
Atopic dermatitis is a chronic inflammatory skin disease involving T-helper (Th) 2 cells, eosinophils, and mast cells. Although CCR4 is a major chemokine receptor expressed on Th2 cells and regarded as a potential therapeutic target for allergic diseases, its role in atopic dermatitis remains unclear. Here, by using a hydrogel patch as a transcutaneous delivery device for ovalbumin (an antigen) and Staphylococcus aureus δ-toxin (a mast cell activator), we efficiently induced acute atopic dermatitis-like skin lesions in BALB/c mice, a strain prone to Th2 responses, which were characterized by increased numbers of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions; elevated levels of total and ovalbumin-specific IgE in the sera; and increased expression of IL-4, IL-17A, IL-22, CCL17, CCL22, and CCR4 in the skin lesions. Of note, the same model was less efficient in C57BL/6 mice, a strain prone to Th1 responses. Using this atopic dermatitis model in BALB/c mice, we demonstrated that CCR4-deficiency or a CCR4 antagonist ameliorated the allergic responses. Collectively, these results demonstrate that CCR4 plays a pivotal role in skin allergic inflammation of BALB/c mice by recruiting CCR4-expressing Th2 cells and Th17 cells., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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