International Immunology, Vol. 13, No. 1, 95-103,
January 2001
© 2001 Japanese Society for Immunology
Inducible expression of a CC chemokine liver- and activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3
/CCL20 by epidermal keratinocytes and its role in atopic dermatitis
Departments of Bacteriology,
1 Dermatology and
4 Surgery, Kinki University School of Medicine, Osaka-Sayama 589-8511, Japan
2 Department of Dermatology, Kobe University School of Medicine, Kobe 650-0011, Japan
3 Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Correspondence to: O. Yoshie
Liverand activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3
/CCL20 is a CC chemokine which is constitutively expressed by follicle-associated epithelial cells in the mucosa, and attracts cells expressing CCR6 such as immature dendritic cells and 4ß7high intestine-seeking memory T cells. Here, we examine LARC/CCL20 expression in the skin. LARC/CCL20 mRNA and protein were induced in primary human keratinocytes upon stimulation with proinflammatory cytokines such as IL-1 and tumor necrosis factor (TNF)-. In mice, intradermal injection of IL-1 and TNF- rapidly induced a local accumulation of transcripts for LARC/CCL20 and its receptor CCR6 with a lag of several hours in the latter. In humans, immunostaining of LARC/CCL20 was weak if any in normal skin tissues but strongly augmented in lesional skin tissues with atopic dermatitis. Furthermore, massive infiltration of cells with markers such as CD1a, CD3 or HLA-DR was present in atopic skin lesions. Many infiltrating cells were also found to be CCR6+ by a newly generated monoclonal anti-CCR6. However, Langerhans cells residing within the epidermis were hardly stained by anti-CCR6 in normal and atopic skin tissues. Furthermore, plasma levels of LARC/CCL20 were found to be elevated in patients with atopic dermatitis. Collectively, our results suggest that epidermal keratinocytes produce LARC/CCL20 upon stimulation with proinflammatory cytokines such as IL-1 and TNF-, and attract CCR6-expressing immature dendritic cells and memory/effector T cells into the dermis of inflamed skin such as atopic dermatitis. LARC/CCL20 may not, however, play a major role in homeostatic migration of Langerhans cells into the skin.
Keywords: chemokine, chemokine receptor, dendritic cells, IL-1, Langerhans cells, skin, tumor necrosis factor
Transmitting editor: M. Miyasaka
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