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

Title: A mechanistic role for leptin in human dendritic cell migration: differences between ileum and colon in health and Crohn's disease
Authors: Al-Hassi, HO
Bernardo, D
Murugananthan, AU
Mann, ER
English, NR
Jones, A
Kamm, MA
Arebi, N
Hart, AL
Blakemore, AI
Stagg, AJ
Knight, SC
Item Type: Journal 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 3beta 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.
Issue Date: 1-Jul-2013
Date of Acceptance: 17-Oct-2012
URI: http://hdl.handle.net/10044/1/63927
DOI: https://dx.doi.org/10.1038/mi.2012.113
ISSN: 1933-0219
Publisher: Nature Publishing Group
Start Page: 751
End Page: 761
Journal / Book Title: Mucosal Immunology
Volume: 6
Issue: 4
Copyright Statement: © 2013 Society for Mucosal Immunology. This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http:// creativecommons.org/licenses/by-nc-nd/3.0
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
INFLAMMATORY-BOWEL-DISEASE
CHEMOKINE RECEPTOR CCR7
MESENTERIC LYMPH-NODES
INTESTINAL INFLAMMATION
STIMULATORY CAPACITY
CYTOKINE PRODUCTION
SIGNALING PATHWAY
ADIPOSE-TISSUE
IN-VITRO
MATURATION
B7-1 Antigen
B7-2 Antigen
CD40 Antigens
Case-Control Studies
Cell Movement
Cellular Microenvironment
Colon
Crohn Disease
Dendritic Cells
Humans
Ileum
Leptin
Receptors, CCR7
Receptors, Leptin
STAT3 Transcription Factor
Antigens, CD40
Antigens, CD80
Antigens, CD86
06 Biological Sciences
11 Medical And Health Sciences
Notes: 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 BB/J004529/1/Biotechnology and Biological Sciences Research Council/United Kingdom Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't United States Mucosal immunology Mucosal Immunol. 2013 Jul;6(4):751-61. doi: 10.1038/mi.2012.113. Epub 2012 Nov 21. 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 3beta 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.
Online Publication Date: 2012-11-21
Appears in Collections:Division of Surgery
Department of Medicine
Faculty of Medicine



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