Identification of Cadherin-26, Its Involvement in Allergic Inflammation, and Development of a Potential Therapeutic

Published Jan. 4, 2017
Mucosal Immunology

Cadherin-26 (CDH26) is the only member of the cadherin family significantly upregulated in human allergic gastrointestinal tissue in both eosinophilic esophagitis (EoE) and eosinophilic gastritis (EG), which may make this protein a novel tool to exploit for developing better treatments for eosinophilic gastrointestinal disorders.

Cadherins are proteins that play important roles in cell adhesion. They contribute to maintaining skin and mucosal barriers by regulating access of pathogens and allergens to underlying tissue and immunocytes. Modulation of cadherin expression and function has been associated with a number of diseases.

In a study led by Julie Caldwell, PhD, and Marc Rothenberg, MD, PhD, investigators analyzed the biochemical, molecular, and functional properties of CDH26. They report that this protein:

• Has an epithelial cell-restricted expression pattern that is particularly prominent following gene induction during allergic inflammation
• Serves as an a4 and aE integrin receptor
• Has the capacity to modulate leukocyte adhesion and activation
• Has immunomodulatory function that can be exploited via a CDH26-Fc fusion protein, which has immunosuppressive activity

These findings could be important to people battling eosinophilic gastritis. While corticosteroids can help manage the condition, so far, there is no cure. An international patent has been granted related to this study's findings.

“We speculate that in addition to mediating adhesion, interaction of epithelial-expressed CDH26 with leukocyte integrins could initiate intracellular signaling in both epithelial cells and leukocytes,” Rothenberg says. “This could impact diverse processes such as alteration of gene expression, regulation of barrier function, or production of mediators by either cell type."