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

H O Al-Hassi, D Bernardo, A U Murugananthan, E R Mann, N R English, A Jones, M A Kamm, N Arebi, Ailsa Hart, Alex Blakemore, A J Stagg, Stella Knight

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)751-61
Number of pages11
JournalMucosal Immunology
Volume6
Issue number4
DOIs
Publication statusPublished - Jul 2013

Keywords

  • B7-1 Antigen/metabolism
  • B7-2 Antigen/metabolism
  • CD40 Antigens/metabolism
  • Case-Control Studies
  • Cell Movement/immunology
  • Cellular Microenvironment/genetics
  • Colon/immunology
  • Crohn Disease/immunology
  • Dendritic Cells/immunology
  • Humans
  • Ileum/immunology
  • Leptin/metabolism
  • Receptors, CCR7/metabolism
  • Receptors, Leptin/biosynthesis
  • STAT3 Transcription Factor/metabolism

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