Cd14 is a Modifier of IBD Development by Influencing the Intestinal Barrier Function

Inflammatory bowel disease (IBD) is characterised by relapsing inflammation of the gut. The pathogenesis of disease still remains unknown. However, intestinal barrier disruption likely plays a key role in IBD development. In a mouse model based on Interleukin-10 (Il10) deficiency Cd14 was suggested as a genetic modifier of colitis susceptibility. Barrier function was analysed in C57BL/6J.129S1-Cd14^tm1Smg (B6-Cd14^-/-) mice as well as in B6.129S1P2-Il10^tm1CgnCd14^tm1Smg (B6-Il10^-/-Cd14^-/-) mice, a model of chronic colitis. Intestinal permeability was investigated in vivo by intestinal FITC-dextran uptake and in vitro by qRT-PCR of Tight-Junction-Proteins (TJ) and immunohistological staining of Occludin, Ki67 and TUNEL apoptosis assay. Severity of intestinal inflammation was evaluated histologically and TNFα and IFNγ gene expressions were quantified by qRT-PCR. B6-Cd14^-/- mice showed no differences in this experimental setup compared to wildtype controls. However, FITC-dextran uptake was increased and TJ expression was decreased in B6-Il10^-/-Cd14^-/-mice compared to Il10-deficient mice. Likewise immunohistology indicated a barrier disruption of the B6-Il10^-/-Cd14^-/- mice. Histology and inflammatory cytokine expression revealed increased intestinal inflammation in B6-Il10^-/-Cd14^-/-mice. Cd14 deficiency seems to have no influence on epithelial tightness under steady state conditions but it presumably untightens the intestinal barrier under inflammatory conditions. In conclusion Cd14 influences IBD development by modulating the intestinal barrier function.