Macrophage inflammatory protein 3α is expressed at inflamed epithelial surfaces and is the most potent chemokine known in attracting Langerhans cell precursors

Dendritic cells (DCs) form a network comprising different populations that initiate and differentially regulate immune responses. Langerhans cells (LCs) represent a unique population of DCs colonizing epithelium, and we present here observations suggesting that macrophage inflammatory protein (MIP)-3 alpha plays a central role in LC precursor recruitment into the epithelium during inflammation. (a) Among DC populations, MIP-3 alpha was the most potent chemokine inducing the selective migration of in vitro-generated CD34(+) hematopoietic progenitor cell-derived LC precursors and skin LCs in accordance with the restricted MIP-3 alpha receptor (CC chemokine receptor 6) expression to these cells. (b) MIP-3 alpha was mainly produced by epithelial cells, and the migration of LC precursors induced by the supernatant of activated skin keratinocytes was completely blocked with an antibody against MIP-3 alpha. (c) In vivo, MIP-3 alpha was selectively produced at sites of inflammation as illustrated in tonsils and lesional psoriatic skin where MIP-3 alpha upregulation appeared associated with an increase in LC turnover. (d) Finally, the secretion of MIP-3 alpha was strongly upregulated by cells of epithelial origin after inflammatory stimuli (interleukin 1 beta plus tumor necrosis factor or) or T cell signals. Results of this study suggest a major role of MIP-3 alpha in epithelial colonization by LCs under inflammatory conditions and immune disorders, and might open new ways to control epithelial immunity.