Keratinocyte-derived monocyte chemoattractant protein 1 (MCP-1): analysis in a transgenic model demonstrates MCP-1 can recruit dendritic and Langerhans cells to skin.
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.
Nakamura
K
K
Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Williams
I R
IR
Kupper
T S
TS
D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D003877:Dermatitis, Contact / Q000503:physiopathology; D004525:Efferent Pathways / Q000503:physiopathology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D015603:Keratinocytes / Q000737:chemistry*; D007801:Langerhans Cells / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism*; D012867:Skin / Q000166:cytology
D018932:Chemokine CCL2; D000949:Histocompatibility Antigens Class II