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NOD2-expressing bone marrow-derived cells appear to regulate epithelial innate immunity of the transplanted human small intestine.

Abstract：

BACKGROUND:Intestinal allograft rejection resembles Crohn's disease clinically and pathologically. An understanding of its mechanism could impact this life-saving procedure, as well as provide insight into the pathophysiology of inflammatory bowel disease. The NOD2 protein has been implicated as a key player in intestinal immune health, as a consequence of the discovery of three polymorphisms linked with Crohn's disease. An investigation was carried out to determine whether epithelial immune function and graft survival were influenced by NOD2 mutations in an intestinal transplant population. METHODS:The NOD2 genotypes of 34 transplants performed consecutively over the past 3 years were determined. The NOD2 genotypes were related to clinical outcomes and the expression of certain intestinal antimicrobial peptides (AMPs) believed to protect the epithelium. RESULTS:An unexpectedly high percentage of recipients, 35%, possessed NOD2 polymorphisms, while 8.6% of donors had comparable mutations. The likelihood of allograft failure was about 100-fold higher in recipients with mutant NOD2 alleles compared with recipients with wild-type NOD2 loci. Rejection in NOD2 mutant recipients was characterised by decreased expression of certain Paneth cell and enterocyte AMPs, prior to the onset of epithelial injury and inflammation. CONCLUSIONS:Crohn's disease-associated polymorphisms in the NOD2 gene in the recipient represent a critical immunological risk factor for intestinal allograft rejection. Compromised epithelial defences precede visible epithelial injury and inflammatory infiltration. The association of impaired epithelial immunity with the recipient's genotype suggests that certain NOD2-expressing cells of haematopoietic origin play a role in the process, perhaps by regulating expression of certain epithelial AMPs within the allograft.

journal_name

Gut

journal_title

Gut

authors

Fishbein T,Novitskiy G,Mishra L,Matsumoto C,Kaufman S,Goyal S,Shetty K,Johnson L,Lu A,Wang A,Hu F,Kallakury B,Lough D,Zasloff M

doi

10.1136/gut.2007.133322

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

323-30

issue

eissn

0017-5749

issn

1468-3288

pii

gut.2007.133322

journal_volume

pub_type

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NOD2-expressing bone marrow-derived cells appear to regulate epithelial innate immunity of the transplanted human small intestine.