Journal article
A mechanistic role for leptin in human dendritic cell migration: Differences between ileum and colon in health and Crohn's disease
HO Al-Hassi, D Bernardo, AU Murugananthan, ER Mann, NR English, A Jones, MA Kamm, N Arebi, AL Hart, AIF Blakemore, AJ Stagg, SC Knight
Mucosal Immunology | NATURE PUBLISHING GROUP | Published : 2013
DOI: 10.1038/mi.2012.113
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 ..
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Awarded by Ruth K. Broad Biomedical Research Foundation
Funding Acknowledgements
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.