CCR4 Is Critically Involved in Skin Allergic Inflammation of BALB/c Mice

J Invest Dermatol. 2018 Aug;138(8):1764-1773. doi: 10.1016/j.jid.2018.02.027. Epub 2018 Mar 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / administration & dosage
  • Bacterial Toxins / immunology
  • Dermatitis, Atopic / 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 / immunology*
  • Receptors, CCR4 / metabolism
  • Skin / cytology
  • Skin / immunology
  • Skin / pathology
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism


  • Bacterial Toxins
  • Ccr4 protein, mouse
  • Receptors, CCR4
  • staphylococcal delta toxin
  • Ovalbumin