MIG is a Dominant Lymphocyte-Attractant Chemokine in Lichen Planus Lesions

Abstract

Dense accumulation of mononuclear cells (lymphocytes >> macrophages) in the dermal-epidermal interface and a T cell-mediated cytotoxic reaction against basal keratinocytes are hallmarks of lichen planus lesions. In this study, we focused on the chemotactic signals responsible for the selective recruitment of these cells. Using in situ hybridization and immunohistochemistry, the expression and localization of the lymphocyte-and/or monocyte/macrophage-attractant CC chemokines macrophage chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed, and secreted (RANTES), macrophage inflammatory protein-1alpha and -1alpha (MIP-1alpha/beta), I-309 and the CXC chemokines monokine induced by interferon-gamma (MIG), interferon-gamma-inducible protein-10 (IP-10), interleukin-8 (IL-8), epithelial-derived neutrophil attractant-78, and growth-related oncogene-alpha were investigated. Strong mRNA expression of MIG, IP-10, and MCP-1 and moderate mRNA expression of RANTES and MIP-1alpha were detected exclusively within foci characterized by strong infiltration with CD3+ lymphocytes (CD4+ cells > CD8+ cells) and CD68+ macrophages. All other chemokines investigated were minimally expressed or absent. With more than 11% of total cells strongly expressing MIG transcripts, this selectively lymphotactic chemokine was by far the dominant chemokine and thus may significantly contribute to the inflammatory reaction in lichen planus lesions. According to the mRNA expression profiles, MIG, IP-10, and MCP-1 were expressed by both basal keratinocytes above and mononuclear cells within the inflammatory foci. Our findings indicate that a set of chemokines composed of IP-10, MCP-1, RANTES, MIP-1alpha, and especially MIG contributes to the cytokine network and preferential trafficking of mononuclear cells to the interface region of lichen planus lesions.