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Adipokines from local fat cells shape the macrophage compartment of the creeping fat in Crohn's disease
  1. Lea Isabell Kredel1,
  2. Arvind Batra1,
  3. Thorsten Stroh1,
  4. Anja A Kühl2,3,
  5. Martin Zeitz1,
  6. Ulrike Erben1,3,
  7. Britta Siegmund1
  1. 1Medical Department (Gastroenterology, Rheumatology, Infectious Diseases), Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Berlin, Germany
  2. 2Institute for Pathology, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Berlin, Germany
  3. 3Research Center ImmunoSciences, Charité—Universitätsmedizin Berlin, Berlin, Germany
  1. Correspondence to Dr Britta Siegmund, Medical Department (Gastroenterology, Rheumatology, Infectious Diseases), Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Hindenburgdamm 30, 12200 Berlin, Germany; britta.siegmund{at}charite.de

Abstract

Objective The creeping fat in Crohn's disease (CD) is infiltrated by macrophages; local adipokine levels are increased. This study aimed to link these observations to define a role for macrophages in the pathology of human CD.

Methods Human peripheral blood CD14 cells were polarised in vitro into M1 and M2 macrophages. The effects on adipokine receptors, phenotypic surface markers, cytokines and chemokines were assessed after treatment with leptin and adiponectin. Immunohistochemistry visualised macrophage subtypes in samples of mesenteric fat tissue from patients with CD. The chemotactic potential of secreted macrophage products was determined by T cell migration and chemokine production in vitro.

Results Although both adipokines altered the phenotype and function of M1 and M2 macrophages, M2 macrophages were more susceptible. M1 responded to leptin by increased cytokine production, but the stronger effect was seen in M2 macrophages with high expression of interleukin (IL)-10, IL-6 and tumour necrosis factor α. Adiponectin exerted similar effects and led to upregulated mannose receptor expression by M2 macrophages. Large macrophage numbers within the mesenteric fat tissue of patients with CD comprise a unique infiltration predominantly of M2 macrophages, leading to an IL-10-rich environment. While leptin increased the potency of both subtypes to attract CD3 T cells, adiponectin only affected M2 macrophages.

Conclusion The adipocyte-dependent microenvironment within the creeping fat of patients with CD modulates the local macrophage compartment to a preference for the M2 subtype. The findings in this study with human cells suggest a protective role for the mesenteric fat in CD in terms of an enveloping barrier with the potential to limit intestinal inflammation.

  • Adipokines
  • macrophage polarisation
  • Crohn's disease
  • creeping fat
  • macrophages
  • inflammatory bowel disease
  • inflammatory cells
  • mucosal defense
  • T lymphocytes
  • lymphocytic colitis
  • HIV/AIDS
  • mucosal immunology
  • HIV-related gastrointestinal disease
  • leptin
  • IL-18
  • chronic IBD
  • IBD models

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Footnotes

  • Funding The study was supported by the Deutsche Forschungsgemeinschaft, Collaborative Research Center 633 “Induction and modulation of T cell-mediated immune reactions in the gastrointestinal tract” TP A12 (BS), TP Z1 (MZ, AAK), the Integrated Research Training Group Immuco (LIK) and SI 749/6-1 (BS).

  • Competing interests None.

  • Ethics approval The outline of the study was approved by the local ethics committee (approval number EA4/059/10).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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