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

• Published in: Mucosal immunology Vol. 11; no. 2; pp. 345 - 356
• Main Authors: Krug, S M, Bojarski, C, Fromm, A, Lee, I M, Dames, P, Richter, J F, Turner, J R, Fromm, M, Schulzke, J-D
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-03-2018; Elsevier Limited
• Subjects: 631/250/1933; 631/250/249/2510/257/1389; 631/250/516; 631/45/612/1237; Adult; Aged; Allergology; Antibodies; Antigens; Antigens - immunology; Antigens - metabolism; Biomedical and Life Sciences; Biomedicine; Claudin-2 - metabolism; Colitis, Ulcerative - immunology; Colon; Crohn Disease - immunology; Crohn's disease; Cytokines; Down-Regulation; Female; Gastroenterology; HT29 Cells; Humans; Immunology; Inflammation - immunology; Inflammatory bowel disease; Inflammatory bowel diseases; Interleukin 13; Interleukin-13 - metabolism; Interleukin-13 Receptor alpha1 Subunit - metabolism; Interleukin-13 Receptor alpha2 Subunit - metabolism; Intestinal Mucosa - physiology; Intestine; Macromolecular Substances - immunology; Macromolecular Substances - metabolism; Macromolecules; Male; MARVEL Domain Containing 2 Protein - metabolism; Middle Aged; Molecular Targeted Therapy; Signal Transduction; Tight Junctions - metabolism; Ulcerative colitis; Young Adult
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2017.52

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 α1 upregulates claudin-2, whereas IL-13 receptor α2 downregulates Tric. We suggest to target the α2 receptor in future developments of therapeutical IL-13-based biologicals.