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

Summary

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.

Highlights

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  ASCs isolated from CD patients are highly proliferative, invasive, and phagocytic

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  Proliferative ASCs may be responsible for the development of creeping fat

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  ASCs from CD patients have dampened immunosuppressive properties

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  Selection of the best immunosuppressive ASCs for cell therapy is advocated

Abstract

Serena and colleagues show that CD alters the biological function and immune properties of ASCs as adipocyte precursors. They propose that understanding how CD alters ASC functionality is critical for elucidating the complex pathophysiology of this disease, as well as for the success of cell-based therapies. Their work suggests that inhibiting the secretion of IL-1β may represent a novel therapeutic approach in CD.