Cadherin 26 is an alpha integrin-binding epithelial receptor regulated during allergic inflammation

Mucosal Immunol. 2017 Sep;10(5):1190-1201. doi: 10.1038/mi.2016.120. Epub 2017 Jan 4.


Cadherins (CDH) mediate diverse processes critical in inflammation, including cell adhesion, migration, and differentiation. Herein, we report that the uncharacterized cadherin 26 (CDH26) is highly expressed by epithelial cells in human allergic gastrointestinal tissue. In vitro, CDH26 promotes calcium-dependent cellular adhesion of cells lacking endogenous CDHs by a mechanism involving homotypic binding and interaction with catenin family members (alpha, beta, and p120), as assessed by biochemical assays. Additionally, CDH26 enhances cellular adhesion to recombinant integrin α4β7 in vitro; conversely, recombinant CDH26 binds αE and α4 integrins in biochemical and cellular functional assays, respectively. Interestingly, CDH26-Fc inhibits activation of human CD4+ T cells in vitro including secretion of IL-2. Taken together, we have identified a novel functional CDH regulated during allergic responses with unique immunomodulatory properties, as it binds α4 and αE integrins and regulates leukocyte adhesion and activation, and may thus represent a novel checkpoint for immune regulation and therapy via CDH26-Fc.

MeSH terms

  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Adhesion
  • Child
  • Child, Preschool
  • Epithelial Cells / physiology*
  • Female
  • HEK293 Cells
  • Humans
  • Hypersensitivity / immunology*
  • Infant
  • Inflammation / immunology*
  • Integrin alpha Chains / metabolism
  • Integrin alpha4 / metabolism
  • Integrin beta Chains / metabolism
  • Intestinal Mucosa / metabolism*
  • Intestines / pathology
  • Lymphocyte Activation
  • Male
  • Protein Binding
  • Young Adult


  • CDH26 protein, human
  • Cadherins
  • Integrin alpha Chains
  • Integrin beta Chains
  • integrin beta7
  • Integrin alpha4