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

Year: 2012
Type: article
Abstract: 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.
DOI: 10.1038/mi.2012.113
Authors: H O Al-Hassi, D Bernardo, A U Murugananthan, E R Mann, N R English, A Jones, M A Kamm, N Arebi, A L Hart, A I F Blakemore, A J Stagg, S C Knight
Institutions: St Mark's Hospital, Imperial College London, The University of Melbourne, St Vincent's Hospital Melbourne, Queen Mary University of London, Blizard Institute
Language: English
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $4,370
Funders: Eli and Edythe Broad Foundation, Diabetes UK, Imperial College London, Imperial College Healthcare NHS Trust, Medical Research Council, Biotechnology and Biological Sciences Research Council
OpenAlex ID: W2015064334
FWCI: 2.29
Cites: 53
Cited by: 56
Related to: 10