Immunopathogenesis of Crohn's disease.

Thomas T. MacDonald, Antonio DiSabatino, John N. Gordon

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

This review highlights the huge advances made in the understanding of Crohn's disease in the last 15 years. The pathogenic immune response in the gut wall is a highly polarised T helper cell type 1 response, probably directed against antigens of the commensal flora. There is marked over-expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and increased production of matrix degrading enzymes by fibroblasts and macrophages, which are probably responsible for ulceration and fistula formation. Crohn's disease runs in families and the susceptibility genes identified so far are associated with innate recognition of microbial products (Nod2) or epithelial barrier function (OCTN cation transporter genes and DLG5). Endogenous healing pathways mediated by transforming growth factor (TGF)-beta1 are inhibited because mucosal inflammatory cells express Smad7, the endogenous intracellular inhibitor of TGF-beta signalling. This makes it unlikely that enteral feeds containing TFG-beta are therapeutic by means of direct anti-inflammatory effects, however TGF-beta may still be involved because it is a well known epithelial motogen and may promote mucosal healing, in synergy with changes in mucosal bacterial populations as a result of the change in the diet.

Original languageEnglish
JournalJournal of Parenteral and Enteral Nutrition
Volume29
Issue number4 Suppl
Publication statusPublished - Jul 2005

Fingerprint

Crohn disease
transforming growth factor beta
Crohn Disease
Transforming Growth Factor beta
transforming growth factor beta 1
Transforming Growth Factor beta1
Th1 Cells
fistula
enteral feeding
anti-inflammatory activity
Genes
tumor necrosis factor-alpha
Small Intestine
Fistula
fibroblasts
transporters
Cations
cations
macrophages
cytokines

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

Immunopathogenesis of Crohn's disease. / MacDonald, Thomas T.; DiSabatino, Antonio; Gordon, John N.

In: Journal of Parenteral and Enteral Nutrition, Vol. 29, No. 4 Suppl, 07.2005.

Research output: Contribution to journalArticle

MacDonald, Thomas T. ; DiSabatino, Antonio ; Gordon, John N. / Immunopathogenesis of Crohn's disease. In: Journal of Parenteral and Enteral Nutrition. 2005 ; Vol. 29, No. 4 Suppl.
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