Report

Journal of Investigative Dermatology (1995) 105, 635–643; doi:10.1111/1523-1747.ep12324061

Keratinocyte-Derived Monocyte Chemoattractant Protein 1 (MCP-1): Analysis in a Transgenic Model Demonstrates MCP-1 Can Recruit Dendritic and Langerhans Cells to Skin

Koichiro Nakamura, Ifor R Williams and Thomas S Kupper

Harvard Skin Disease Research Center, Division of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, U.S.A.

Received 5 May 1995; Revised 10 July 1995; Accepted 3 August 1995.

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Abstract

Chemokines are thought to play a central role in the recruitment and activation of leukocytes during inflammatory responses. Monocyte chemoattractant protein 1 (MCP-1) is a chemokine of the C-C or beta family that is chemotactic in vitro for monocytes, T cells, and basophils. Its excessive production by keratinocytes has been implicated in psoriasis and other skin diseases. To test the in vivo role of MCP-1 in inflammatory skin disease, we undertook the generation of transgenic mice that express murine MCP-1 in the basal layer of epidermis. Despite production of high levels of functional MCP-1 by basal keratinocytes, documented in vivo and in vitro, these mice did not exhibit spontaneous cutaneous inflammation or any other discernible skin pathology. In contrast, elicited inflammation in the skin of these mice differed qualitatively and quantitatively from that observed in non-transgenic controls. Contact hypersensitivity challenge responses in transgenic animals were characterized by an exaggerated lichenoid infiltration of monocytes and T cells. Additional phenotypic characterization of the normal appearing skin in these mice showed that the only spontaneous change was a dramatic increase and redistribution of CD45+, I-A+ cells that assumed a dendritic morphology in situ, including a subset that expressed markers characteristic of Langerhans cells. Taken together, these data indicate that tissue-specific expression of MCP-1 alone is not sufficient to induce an inflammatory response, though its presence can modify inflammatory and immune events initiated by exogenous stimuli. The recruitment of dendritic and Langerhans cells in the absence of inflammation is a previously unknown consequence of cutaneous MCP-1 production in vivo.

Keywords:

leukocyte migration, T cells, chemokines, epidermis

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