Macrophage inflammatory protein 3 alpha is expressed at inflamed epithelial surfaces and is the most potent chemokine known in attracting Langerhans cell precursors
Mc. Dieu-nosjean et al., Macrophage inflammatory protein 3 alpha is expressed at inflamed epithelial surfaces and is the most potent chemokine known in attracting Langerhans cell precursors, J EXP MED, 192(5), 2000, pp. 705-717
Dendritic cells (DCs) form a network comprising different populations that
initiate and differentially regulate immune responses. Langerhans cells (LC
s) represent a unique population of DCs colonizing epithelium, and we prese
nt here observations suggesting that macrophage inflammatory protein (MIP)-
3 alpha plays a central role in LC precursor recruitment into the epitheliu
m during inflammation. (a) Among DC populations, MIP-3 alpha was the most p
otent chemokine inducing the selective migration of in vitro-generated CD34
(+) hematopoietic progenitor cell-derived LC precursors and skin LCs in acc
ordance with the restricted MIP-3 alpha receptor (CC chemokine receptor 6)
expression to these cells. (b) MIP-3 alpha was mainly produced by epithelia
l cells, and the migration of LC precursors induced by the supernatant of a
ctivated 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 M
IP-3 alpha upregulation appeared associated with an increase in LC turnover
. (d) Finally, the secretion of MIP-3 alpha was strongly upregulated by cel
ls 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 inflam
matory conditions and immune disorders, and might open new ways to control
epithelial immunity.