Macrophage inflammatory protein 3alpha 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)-3alpha plays a central role in LC precursor recruitment into the epithelium during inflammation. (a) Among DC populations, MIP-3alpha 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-3alpha receptor (CC chemokine receptor 6) expression to these cells. (b) MIP-3alpha 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-3alpha. (c) In vivo, MIP-3alpha was selectively produced at sites of inflammation as illustrated in tonsils and lesional psoriatic skin where MIP-3alpha upregulation appeared associated with an increase in LC turnover. (d) Finally, the secretion of MIP-3alpha was strongly upregulated by cells of epithelial origin after inflammatory stimuli (interleukin 1beta plus tumor necrosis factor alpha) or T cell signals. Results of this study suggest a major role of MIP-3alpha in epithelial colonization by LCs under inflammatory conditions and immune disorders, and might open new ways to control epithelial immunity.
Dieu-Nosjean
M C
MC
Laboratory for Immunological Research, Schering-Plough, 69571 Dardilly, France.
Massacrier
C
C
Homey
B
B
Vanbervliet
B
B
Pin
J J
JJ
Vicari
A
A
Lebecque
S
S
Dezutter-Dambuyant
C
C
Schmitt
D
D
Zlotnik
A
A
Caux
C
C
D000818:Animals; D002460:Cell Line; D054418:Chemokine CCL20; D019742:Chemokines, CC; D004848:Epithelium / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007801:Langerhans Cells / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011565:Psoriasis / Q000378:metabolism; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000032:analysis; D013234:Stem Cells / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine