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Tricellulin is regulated via interleukin-13-receptor ?2, affects macromolecule uptake, and is decreased in ulcerative colitis.


ABSTRACT: In the two inflammatory bowel diseases, ulcerative colitis (UC) and Crohn's disease (CD), altered expression of tight junction (TJ) proteins leads to an impaired epithelial barrier including increased uptake of luminal antigens supporting the inflammation. Here, we focused on regulation of tricellulin (Tric), a protein of the tricellular TJ essential for the barrier against macromolecules, and hypothesized a role in paracellular antigen uptake. We report that Tric is downregulated in UC, but not in CD, and that its reduction increases the passage of macromolecules. Using a novel visualization method, passage sites were identified at TJ regions usually sealed by Tric. We show that interleukin-13 (IL-13), beyond its known effect on claudin-2, downregulates Tric expression. These two effects of IL-13 are regulated by different signaling pathways: The IL-13 receptor ?1 upregulates claudin-2, whereas IL-13 receptor ?2 downregulates Tric. We suggest to target the ?2 receptor in future developments of therapeutical IL-13-based biologicals.

SUBMITTER: Krug SM 

PROVIDER: S-EPMC5730503 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Tricellulin is regulated via interleukin-13-receptor α2, affects macromolecule uptake, and is decreased in ulcerative colitis.

Krug S M SM   Bojarski C C   Fromm A A   Lee I M IM   Dames P P   Richter J F JF   Turner J R JR   Fromm M M   Schulzke J-D JD  

Mucosal immunology 20170614 2


In the two inflammatory bowel diseases, ulcerative colitis (UC) and Crohn's disease (CD), altered expression of tight junction (TJ) proteins leads to an impaired epithelial barrier including increased uptake of luminal antigens supporting the inflammation. Here, we focused on regulation of tricellulin (Tric), a protein of the tricellular TJ essential for the barrier against macromolecules, and hypothesized a role in paracellular antigen uptake. We report that Tric is downregulated in UC, but not  ...[more]

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