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Co-Culture of Murine Small Intestine Epithelial Organoids with Innate Lymphoid Cells
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Co-Culture of Murine Small Intestine Epithelial Organoids with Innate Lymphoid Cells

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Interleukin-9 production by type 2 innate lymphoid cells induces Paneth cell metaplasia and small intestinal

Chengyin Yuan1, Aditya Rayasam1, Alison Moe1

  • 1Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.

Nature Communications
|December 2, 2023
PubMed

Insights

Chronic myelogenous leukemia (CML) can induce Paneth cell metaplasia (PCM) in the gut. This occurs through an extra-intestinal inflammatory pathway involving IL-33 and IL-9, impacting gastrointestinal epithelial cell fate.

Area of Science:

  • Gastroenterology
  • Immunology
  • Oncology

Background:

  • Paneth cell metaplasia (PCM) is often associated with gastrointestinal (GI) diseases, but the underlying mechanisms and triggers are not fully understood.
  • It remains unclear if PCM development is exclusively initiated by intrinsic GI tract disorders.

Purpose of the Study:

  • To investigate the mechanistic pathway of Paneth cell metaplasia (PCM) development.
  • To determine if extra-intestinal diseases can initiate PCM.

Main Methods:

  • Development of a murine model for chronic myelogenous leukemia (CML) using an inducible bcr-abl oncogene.
  • Analysis of the inflammatory state within the GI tract and immune cell involvement (ILC2s, mast cells).
  • Assessment of cytokine production (IL-33, IL-9) and its effect on intestinal epithelial cells.

Main Results:

  • CML induced a proinflammatory state in the GI tract, leading to epithelial IL-33 production.
  • IL-33 triggered type 2 innate lymphoid cells (ILC2s) to produce IL-9.
  • IL-9 was identified as the direct inducer of PCM in the colon and caused tissue remodeling in the small intestine.

Conclusions:

  • An extra-intestinal disease (CML) can trigger an immune circuit (ILC2/IL-9) to induce Paneth cell metaplasia (PCM).
  • This pathway demonstrates that GI epithelial cell fate can be regulated by systemic conditions.
  • The findings reveal a novel mechanism linking CML to gastrointestinal pathology.

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