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PMID: 10974036 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of experimental medicine ·Vol. 192 ·No. 5 ·2000-09-04 ·Pages 705-18

Dieu-Nosjean MC, Massacrier C, Homey B, Vanbervliet B, Pin JJ, Vicari A, Lebecque S, Dezutter-Dambuyant C, Schmitt D, Zlotnik A, Caux C

Abstract

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.

MeSH Terms
Animals Cell Line Chemokine CCL20 Chemokines, CC Epithelium/chemistry Humans Inflammation/metabolism Langerhans Cells/physiology Macrophage Inflammatory Proteins/analysis,physiology Mice Mice, Inbred BALB C Psoriasis/metabolism Receptors, CCR6 Receptors, Chemokine/analysis Stem Cells/physiology T-Lymphocytes/physiology
Chemicals
CCL20 protein, human CCR6 protein, human Chemokine CCL20 Chemokines, CC Macrophage Inflammatory Proteins Receptors, CCR6 Receptors, Chemokine
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Dieu-Nosjean M C
Laboratory for Immunological Research, Schering-Plough, 69571 Dardilly, France.
Massacrier C
Homey B
Vanbervliet B
Pin J J
Vicari A
Lebecque S
Dezutter-Dambuyant C
Schmitt D
Zlotnik A
Caux C
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.192.5.705
Published
2000-09-04
Pages
705-18
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193271
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.192.5.705 PMC Full Text View journal details
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