Interleukin-13 Is the Key Effector Th2 Cytokine in Ulcerative Colitis That Affects Epithelial Tight Junctions, Apoptosis, and Cell Restitution

Abstract

IL-13 was identified as an important effector cytokine in UC that impairs epithelial barrier function by affecting epithelial apoptosis, tight junctions, and restitution velocity.

Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis

“…Expression of the major tight junction proteins is also reduced in the intestines of GC-C deficient mice. Luminal antigens permeate the defective barrier, promote inflammation, and damage the intestinal mucosal architecture [18,41] . These studies suggest a critical role of GC-C signaling in preserving the intestinal integrity.…”

Helminths and intestinal barrier function

“…68 The drop in TER in secondary infections with H. polygyrus, was accompanied by a small increase in the epithelial expression of the pore-forming claudin-2, and the barrier defect was absent in IL-13Ra1 ¡/¡ mice. 69 Increased IL-13 production following infection with helminths can be from innate 70 or adaptive immune cells, 71 and while IL-13 has been shown to directly decrease the barrier function of epithelial monolayers in vitro, 24,72 it is unclear if helminth-evoked IL-13 targets the epithelium directly or via other immunoregulatory activities.…”

ClC-2 regulation of intestinal barrier function: Translation of basic science to therapeutic target

“…49 Dysregulation of tight junction proteins contributes to barrier loss in patients with intestinal diseases. For instance, claudin-2, a pore forming tight junction protein, was significantly upregulated in CD, 47 UC, 50 and in patients with collagenous colitis 51 by a Th2 cell cytokine (IL-13)-dependent mechanism. Occludin and select sealing claudins (claudins-1, 3, and 4) were reduced in expression or redistributed in intestinal permeability disorders, including ischemic injury, 8 CD, 47 and UC.…”

“…47,48,50 Thus, we hypothesized that the ClC-2 chloride channel also has a critical role in the regulation of colonic barrier function under inflammatory conditions. Our recent study found that the severity of experimental colitis was significantly increased in the ClC-2 ¡/¡ mice as compared with WT mice.…”