title: A mechanistic role for leptin in human dendritic cell migration: differences between ileum and colon in health and Crohn's disease.
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.
authors.affiliation: Antigen Presentation Research Group, Department of Medicine, Imperial College London, Northwick Park and St Mark's Hospitals, Harrow, UK.
authors.forename: H O
authors.initials: HO
authors.lastname: Al-Hassi
authors.forename: D
authors.initials: D
authors.lastname: Bernardo
authors.forename: A U
authors.initials: AU
authors.lastname: Murugananthan
authors.forename: E R
authors.initials: ER
authors.lastname: Mann
authors.forename: N R
authors.initials: NR
authors.lastname: English
authors.forename: A
authors.initials: A
authors.lastname: Jones
authors.forename: M A
authors.initials: MA
authors.lastname: Kamm
authors.forename: N
authors.initials: N
authors.lastname: Arebi
authors.forename: A L
authors.initials: AL
authors.lastname: Hart
authors.forename: A I F
authors.initials: AI
authors.lastname: Blakemore
authors.forename: A J
authors.initials: AJ
authors.lastname: Stagg
authors.forename: S C
authors.initials: SC
authors.lastname: Knight
mesh_terms: D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D002465:Cell Movement / Q000276:immunology*; D060833:Cellular Microenvironment / Q000235:genetics / Q000276:immunology; D003106:Colon / Q000276:immunology / Q000378:metabolism; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D054400:Receptors, CCR7 / Q000378:metabolism; D054411:Receptors, Leptin / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D020738:Leptin; D054400:Receptors, CCR7; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor