CCL17 transgenic mice show an enhanced Th2‐type response to both allergic and non‐allergic stimuli
Open Access
- 27 July 2006
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 36 (8), 2116-2127
- https://doi.org/10.1002/eji.200535564
Abstract
CC chemokine ligand (CCL)17 is implicated in the pathogenesis of atopic dermatitis (AD). To study the effect of CCL17 produced by keratinocytes (KC) during inflammation, we created transgenic (Tg) mice in which CCL17 is overexpressed in KC. Th2‐type contact hypersensitivity (CHS) was enhanced and Th1‐type CHS was suppressed in these mice. Increased numbers of CC chemokine receptor (CCR)4+ cells and mast cells infiltrated in Tg mice. Levels of IL‐4 mRNA were higher and those of IFN‐γ mRNA were lower in both acute and chronic CHS. Higher levels of serum IgE were observed after CHS. Numbers of CCR4+ cells among PBMC were increased in Tg mice challenged acutely on the trunk. Chronic irritation with croton oil induced dermatitis and an elevation of serum IgE levels. Tg mice showed enhanced ear swelling after tape stripping. CCL17 was thought to modify the inflammation caused by sensitizing reagents as well as irritant reagents by attracting CCR4+ cells into the lesional skin and creating a Th2‐dominant condition. AD‐like conditions such as increased number of mast cells and elevated levels of serum IgE were observed. Thus, CCL17 may participate in the pathogenesis of skin diseases such as AD by regulating both allergic and irritant inflammation.Keywords
This publication has 51 references indexed in Scilit:
- Expression of CS-1 fibronectin precedes monocyte chemoattractant protein-1 production during elicitation of allergic contact dermatitisClinical and Experimental Allergy, 2003
- AWD 12–281, a highly selective phosphodiesterase 4 inhibitor, is effective in the prevention and treatment of inflammatory reactions in a model of allergic dermatitisJournal of Pharmacy and Pharmacology, 2003
- Compartmentalized Production of CCL17 In VivoThe Journal of Experimental Medicine, 2003
- CC Chemokine Receptor (CCR)4 and the CCR10 Ligand Cutaneous T Cell–attracting Chemokine (CTACK) in Lymphocyte Trafficking to Inflamed SkinThe Journal of Experimental Medicine, 2001
- The Role of CTLA-4 in Murine Contact HypersensitivityJournal of Investigative Dermatology, 2001
- Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activityJournal of Allergy and Clinical Immunology, 2001
- Molecular Cloning of Murine CC CKR-4 and High Affinity Binding of Chemokines to Murine and Human CC CKR-4Biochemical and Biophysical Research Communications, 1996
- Keratinocyte-Derived Monocyte Chemoattractant Protein 1 (MCP-1): Analysis in a Transgenic Model Demonstrates MCP-1 Can Recruit Dendritic and Langerhans Cells to SkinJournal of Investigative Dermatology, 1995
- Perturbation of epidermal barrier function correlates with initiation of cytokine cascade in human skinJournal of the American Academy of Dermatology, 1994
- Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigmCell, 1994