Macrophage Inflammatory Protein 3 a 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 a plays a central role in LC precursor recruitment into the epithelium during inflammation. (a) Among DC populations, MIP-3 a was the most potent chemokine inducing the selective migration of in vitro–generated CD34 1 hematopoietic progenitor cell–derived LC precursors and skin LCs in accordance with the restricted MIP-3 a receptor (CC chemokine receptor 6) expression to these cells. (b) MIP-3 a 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 a . (c) In vivo, MIP-3 a was selectively produced at sites of inflammation as illustrated in tonsils and lesional psoriatic skin where MIP-3 a upregulation appeared associated with an increase in LC turnover. (d) Finally, the secretion of MIP-3 a was strongly upregulated by cells of epithelial origin after inflammatory stimuli (interleukin 1 b plus tumor necrosis factor a ) or T cell signals. Results of this study suggest a major role of MIP-3 a in epithelial colonization by LCs under inflammatory conditions and immune disorders, and might open new ways to control epithelial immunity.