Intestinal expression of SHIP in inflammatory bowel diseases
| Autor: | Jan Van der Goten, Severine Vermeire, Gert De Hertogh, Ingrid Arijs, Paul Rutgeerts, Frans Schuit, Bart Lemmens |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
INPP5D Gene
immunoregulation animal diseases T cell Biology chemistry.chemical_compound Crohn Disease medicine Animals bone marrow chimera genetics Ileitis Receptor chemistry.chemical_classification Inflammatory Bowel Disease technology industry and agriculture Gastroenterology food and beverages cell signalling crohn's colitis Tyrosine phosphorylation medicine.disease Phosphoric Monoester Hydrolases Cell biology Crohn's disease Haematopoiesis Enzyme medicine.anatomical_structure chemistry Immunology mucosal immunity SHIP signal transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Gut |
| ISSN: | 1468-3288 0017-5749 |
| DOI: | 10.1136/gutjnl-2011-301256 |
| Popis: | Background Inflammatory bowel disease (IBD) can arise from genetic mutations that compromise intestinal epithelial cell integrity or immune regulation. SHIP has previously been shown to play a pivotal role in limiting the number of immunoregulatory cells and their function. Aim To determine whether SHIP plays a pivotal role in control of immune tolerance in the gut mucosa. Methods Gastrointestinal pathology was assessed in three separate strains of SHIP-deficient mice and their respective wild-type (WT) littermates. Gastrointestinal pathology was analysed in SHIP-deficient hosts reconstituted with WT haematopoietic cell grafts, and WT hosts reconstituted with SHIP-deficient haematopoietic cell grafts including whole splenocytes, purified T cells or natural killer (NK) cells. Major immune cell populations were also analysed in the small intestine of SHIP-deficient mice and WT controls. Results SHIP-deficient mice developed segmental, transmural pyo-granulomatous ilietis that recapitulated classical features of Crohn's disease enteric pathology. Analysis of haematopoietic chimeras showed that WT bone marrow reconstitution of SHIP−/− hosts corrects ileitis. Reconstitution with SHIP−/− splenocytes transferred ileitis to WT hosts. Adoptive transfer of purified SHIP−/− T cells or NK cells to WT hosts did not transfer ileitis. There was a paucity of both CD4 and CD8 T cells in the small intestines of SHIP-deficient mice; however, neutrophil numbers were significantly increased. Conclusions SHIP plays a pivotal role in immune function in the intestine; further scrutiny of this pathway in IBD patients is warranted. It is proposed that SHIP-deficient ileitis results from a local deficit in mucosal T cell immunity that promotes a damaging granulocyte–monocyte inflammation of the distal ileum. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|