Recent evidence has linked intestinal permeability to mucosal inflammation, but molecular studies are lacking. Candidate regulatory molecules localized within the tight junction (TJ) include Junctional Adhesion Molecule (JAM-A), which has been implicated in the regulation of barrier function and leukocyte migration. Thus, we analyzed the intestinal mucosa of JAM-A-deficient (JAM-A-/-) mice for evidence of enhanced permeability and inflammation. Colonic mucosa from JAM-A-/- mice had normal epithelial architecture but increased polymorphonuclear leukocyte infiltration and large lymphoid aggregates not seen in wild-type controls. Barrier function experiments revealed increased mucosal permeability, as indicated by enhanced dextran flux, and decreased transepithelial electrical resistance in JAM-A-/- mice. The in vivo observations were epithelial specific, because monolayers of JAM-A-/- epithelial cells also demonstrated increased permeability. Analyses of other TJ components revealed increased expression of claudin-10 and -15 in the colonic mucosa of JAM-A-/- mice and in JAM-A small interfering RNA - treated epithelial cells. Given the observed increase in colonic inflammation and permeability, we assessed the susceptibility of JAM-A-/- mice to the induction of colitis with dextran sulfate sodium (DSS). Although DSS-treated JAM-A-/- animals had increased clinical disease compared with controls, colonic mucosa showed less injury and increased epithelial proliferation. These findings demonstrate a complex role of JAM-A in intestinal homeostasis by regulating epithelial permeability, inflammation, and proliferation. JEM © The Rockefeller University Press.
CITATION STYLE
Laukoetter, M. G., Nava, P., Lee, W. Y., Severson, E. A., Capaldo, C. T., Babbin, B. A., … Parkos, C. A. (2007). JAM-A regulates permeability and inflammation in the intestine in vivo. Journal of Experimental Medicine, 204(13), 3067–3076. https://doi.org/10.1084/jem.20071416
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