Alphavbeta6 is required in maintaining the intestinal epithelial barrier function

Abstract

Epithelial barrier dysfunction is involved in a large number of diseases, but the pathogenesis is unclear. Integrin alphavbeta6 (avb6) in involved in the maintenance of the mucosal homeostasis. We have investigated the role of avb6 in maintaining the epithelial barrier function. Using T84 monolayers cultures, transepithelial electric resistance (TER) and permeability to ovalbumin (OVA) were measured as indicators of functioning. The antigenicity of OVA collected from the Transwell basal chambers was assessed using OVA-specific T cell proliferation. Knockdown of the avb6 genes increased the permeability of T84 monolayers to OVA, but did not affect TER. The deficiency of avb6-related hyperpermeability in T84 monolayers could be compensated by adding exogenous avb6 to the culture. The OVA samples collected from the basal chambers had strong antigenicity as it markedly induced the antigen specific T cell proliferation. Addition of recombinant avb6 blocked increases in permeability of T84 monolayers to OVA induced by tumor necrosis factor-α.

Notch controls urothelial integrity in the mouse bladder

“…This is in agreement with previous reports implicating TJ proteins in intestinal permeability (31). Interestingly, α v β 6 integrin, which is required for maintaining intestinal barrier function (16), is downregulated in patients with inflammatory bowel disease (IBD) (32). In addition, loss of the hemidesmosome α 6 β 4 integrin leads to loss of epithelial integrity and denudation (33)(34)(35), while inactivation of β 1 integrin, the partner of α 4 integrin, in mice leads to neonatal lethality from dehydration due to defects in the skin barrier (36).…”

“…Molecular analysis of human and animal bladder tissue samples has indicated that reduced expression of the TJ protein zonula occludens-1 (ZO-1) (12) as well as several extracellular matrix (ECM) proteoglycans, such as chondroitin sulfate, perlecan, biglycan, and decorin, is associated with human and feline interstitial cystitis (IC) (13,14), highlighting the importance of cell-cell and cell-ECM interactions in urothelial integrity and barrier functionality. Mouse studies have uncovered roles for ZO-1 in normal intestinal cell shedding and intestinal barrier reestablishment (15), while loss of α v β 6 integrin leads to enterocyte shedding and compromised intestinal barrier (16). IC/bladder pain syndrome (IC/BPS) is a chronic inflammatory…”

Identification of an Anti–Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis

“…A previous study showed induction of integrin avb6 in epithelial cells during wound healing, 14 which may have important roles in epithelial barrier function and mucosal healing. 16 In this study, we also observed stronger expression of avb6 integrins in patients with UC compared with controls. Interestingly, we found that UC patient IgG blocked integrin avb6-fibronectin binding through an RGD motif and inhibited adhesion of HT-29 cells.…”

“…15 Integrin avb6 is reported to play an important role in maintaining epithelial barrier functions. 16 Considering the epithelial barrier defects in UC, we hypothesized that patients with UC may have autoantibodies against epithelial adhesion molecules and thus focused on integrin family proteins in this study. We screened 23 integrin family proteins using enzyme-linked immunosorbent assays (ELISAs) and identified antiintegrin avb6 autoantibodies in the sera of patients with UC.…”

Transgenic overexpression of ITGB6 in intestinal epithelial cells exacerbates dextran sulfate sodium‐induced colitis in mice

“…Unlike α4β7, which is highly expressed in circulating lymphocytes, αvβ6 is an epithelium‐restricted cell surface receptor and is highly expressed in IECs. It was also reported to be dramatically upregulated in response to inflammatory stimuli 15,16,31,32 . Generally, IBD is considered to exhibit the remarkable property of hyperactivation of inflammatory processes, characterized by the production of pro‐inflammatory cytokines and chemokines, and recruitment and activation of intestinal immune cells 33 .…”