Intestinal inflammatory diseases, four of which are discussed here, are associated with alterations of
claudins. In
ulcerative colitis,
diarrhea and
antigen entry into the mucosa occurs.
Claudin-2 is upregulated but data on other
claudins are still limited or vary (e.g.,
claudin-1 and -4). Apart from that, tight junction changes contribute to
diarrhea via a leak flux mechanism, while protection against
antigen entry disappears behind epithelial gross lesions (erosions) and apoptotic foci.
Crohn's disease is additionally characterized by a
claudin-5 and
claudin-8 reduction which plays an active role in
antigen uptake already before gross lesions appear. In
microscopic colitis (MC), upregulation of
claudin-2 expression is weak and a reduction in
claudin-4 may be only passively involved, while
sodium malabsorption represents the main diarrheal mechanism. However,
claudin-5 is removed from MC tight junctions which may be an active trigger for
inflammation through
antigen uptake along the so-called leaky gut concept. In
celiac disease, primary barrier defects are discussed in the context of candidate genes as PARD3 which regulate cell polarity and tight junctions. The loss of
claudin-5 allows small
antigens to invade, while the reductions in others like
claudin-3 are rather passive events. Taken together, the specific role of single
tight junction proteins for the onset and perpetuation of
inflammation and the recovery from these diseases is far from being fully understood and is clearly dependent on the stage of the disease, the background of the other tight junction components, the transport activity of the mucosa, and the presence of other barrier features like gross lesions, an orchestral interplay which is discussed in this article.