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

�� 2012 The Authors. Published by Springer Nature. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher���s website: https://doi.org/10.1038/mi.2012.113Dendritic 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 3�� 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. �� 2013 Society for Mucosal Immunology.We thank The Broad Medical Research Program of the Broad Foundation, USA, the Medical Research Council Trust, UK, St Mark���s Hospital Foundation, UK, the Biotechnology and Biological Research Council Institute Strategic Program for Gut Health and Food Safety BB/J004529/1 and the Brigid Balfour Fund for funding this study. A.I.F.B. is also funded by Diabetes UK and the BRC at the Imperial College Healthcare Trust.Published versio