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Immunopathogenesis of Crohn's Disease
Author(s) -
MacDonald Thomas T.,
DiSabatino Antonio,
Gordon John N.
Publication year - 2005
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/01486071050290s4s118
Subject(s) - nod2 , immunology , crohn's disease , immune system , biology , transforming growth factor , tumor necrosis factor alpha , innate immune system , intracellular , inflammation , disease , microbiology and biotechnology , medicine , pathology
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)‐a 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)‐β1 are inhibited because mucosal inflammatory cells express Smad7, the endogenous intracellular inhibitor of TGF‐β signalling. This makes it unlikely that enteral feeds containing TFG‐β are therapeutic by means of direct anti‐inflammatory effects, however TGF‐β 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.