SHIP deficiency causes Crohn's disease-like ileitis

William G Kerr ¹, Mi-Young Park , Monique Maubert

⁰SUNY Upstate Medical University, 750 E. Adams Street, 2204 Weiskotten Hall, Syracuse, NY 13210, USA. kerrw@upstate.edu

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October 14, 2010

View abstract on PubMed

Summary

The study reveals that SHIP deficiency causes inflammatory bowel disease (IBD) in mice, mimicking Crohn's disease. This immune dysfunction stems from altered T cell populations and increased neutrophils in the gut.

Area Of Science

Immunology
Gastroenterology
Molecular Biology

Background

Inflammatory bowel disease (IBD) pathogenesis involves genetic factors affecting intestinal epithelial integrity and immune regulation.
The SHIP protein is known to limit immunoregulatory cell numbers and function.

Purpose Of The Study

To investigate the role of SHIP in maintaining immune tolerance within the gut mucosa.
To determine if SHIP deficiency contributes to the development of IBD-like pathology.

Main Methods

Assessment of gastrointestinal pathology in SHIP-deficient and wild-type (WT) mice.
Analysis of bone marrow chimeras involving WT and SHIP-deficient hematopoietic stem cells, splenocytes, T cells, and NK cells.
Quantification of immune cell populations in the small intestine of SHIP-deficient and WT mice.

Main Results

SHIP-deficient mice exhibited segmental, transmural pyo-granulomatous ileitis, characteristic of Crohn's disease.
Reconstitution of SHIP-deficient hosts with WT bone marrow corrected ileitis, while SHIP-deficient splenocytes transferred ileitis to WT hosts.
SHIP deficiency led to a decrease in CD4 and CD8 T cells but a significant increase in neutrophils in the small intestine.

Conclusions

SHIP is crucial for intestinal immune function and its pathway warrants investigation in IBD patients.
SHIP-deficient ileitis is proposed to result from impaired mucosal T cell immunity, leading to granulocyte-monocyte inflammation in the distal ileum.

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