A mechanistic role for leptin in human dendritic cell migration: differences between ileum and colon in health and Crohn's disease

Dendritic cells (DC) migrate to lymph nodes on expression of C-C motif chemokine receptor 7 (CCR7) and control immune activity. Leptin, an immunomodulatory adipokine, functions via leptin receptors, signaling via the long isoform of receptor, LepRb. Leptin promotes DC maturation and increases CCR7 e...

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Bibliographic Details
Published in:Mucosal immunology 2013-07, Vol.6 (4), p.751-761
Main Authors: Al-Hassi, H O, Bernardo, D, Murugananthan, A U, Mann, E R, English, N R, Jones, A, Kamm, M A, Arebi, N, Hart, A L, Blakemore, A I F, Stagg, A J, Knight, S C
Format: Article
Language:English
Subjects:
B7-1 Antigen - metabolism
B7-2 Antigen - metabolism
Case-Control Studies
CD40 Antigens - metabolism
Cell Movement - immunology
Cellular Microenvironment - genetics
Cellular Microenvironment - immunology
Colon - immunology
Colon - metabolism
Crohn Disease - immunology
Crohn Disease - metabolism
Dendritic Cells - immunology
Dendritic Cells - metabolism
Humans
Ileum - immunology
Ileum - metabolism
Leptin - metabolism
Receptors, CCR7 - metabolism
Receptors, Leptin - biosynthesis
STAT3 Transcription Factor - metabolism
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Summary:Dendritic cells (DC) migrate to lymph nodes on expression of C-C motif chemokine receptor 7 (CCR7) and control immune activity. Leptin, an immunomodulatory adipokine, functions via leptin receptors, signaling via the long isoform of receptor, LepRb. Leptin promotes DC maturation and increases CCR7 expression on blood DC. Increased mesenteric fat and leptin occur early in Crohn's disease (CD), suggesting leptin-mediated change in intestinal CCR7 expression on DC as a pro-inflammatory mechanism. We have demonstrated CCR7 expression and capacity to migrate to its ligand macrophage inflammatory protein 3β in normal human ileal DC but not colonic or blood DC. In CD, functional CCR7 was expressed on DC from all sites. Only DC populations containing CCR7-expressing cells produced LepRb; in vitro exposure to leptin also increased expression of functional CCR7 in intestinal DC in a dose-dependent manner. In conclusion, leptin may regulate DC migration from gut, in homeostatic and inflammatory conditions, providing a link between mesenteric obesity and inflammation.
ISSN:1933-0219
1935-3456
DOI:10.1038/mi.2012.113