Crohn's Disease Disturbs the Immune Properties of Human Adipose-Derived Stem Cells Related to Inflammasome Activation

Stem Cell Reports. 2017 Oct 10;9(4):1109-1123. doi: 10.1016/j.stemcr.2017.07.014. Epub 2017 Sep 28.

Abstract

Crohn's disease (CD) is characterized by the expansion of mesenteric fat, also known as "creeping fat." We explored the plasticity and immune properties of adipose-derived stem cells (ASCs) in the context of CD as potential key players in the development of creeping fat. Mesenteric CD-derived ASCs presented a more proliferative, inflammatory, invasive, and phagocytic phenotype than equivalent cells from healthy donors, irrespective of the clinical stage. Remarkably, ASCs from the subcutaneous depot of patients with CD also showed an activated immune response that was associated with a reduction in their immunosuppressive properties. The invasive phenotype of mesenteric CD ASCs was governed by an inflammasome-mediated inflammatory state since blocking inflammasome signaling, mainly the secretion of interleukin-1β, reversed this characteristic. Thus, CD alters the biological functions of ASCs as adipocyte precursors, but also their immune properties. Selection of ASCs with the best immunomodulatory properties is advocated for the success of cell-based therapies.

Keywords: cell therapy; creeping fat; immunity; interleukin 1B; invasion; lymphocytes; mesenchymal stem cells; migration; phagocytosis; regulatory T cell.

MeSH terms

  • Adipogenesis / genetics
  • Adipose Tissue / cytology*
  • Adult
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Crohn Disease / immunology*
  • Crohn Disease / metabolism*
  • Cytokines / metabolism
  • Female
  • Glycolysis
  • Humans
  • Immunomodulation
  • Inflammasomes / metabolism*
  • Inflammation Mediators / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Middle Aged
  • Phagocytosis / immunology
  • Phenotype
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Cytokines
  • Inflammasomes
  • Inflammation Mediators