Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
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.
钙黏蛋白（CDH）介导多种炎症过程，包括细胞黏附、迁移和分化。在此，我们报告了未被描述的钙黏蛋白 26（CDH26）在人类过敏胃肠组织的上皮细胞中高度表达。在体外，通过生化测定，CDH26 通过同种型结合和与连环蛋白家族成员（α、β 和 p120）相互作用的机制，促进缺乏内源性 CDH 的细胞中钙依赖性细胞黏附。此外，CDH26 增强细胞对重组整合素 α4β7 的黏附性；相反，重组 CDH26 在生化和细胞功能测定中分别与αE 和 α4 整合素结合。有趣的是，CDH26-Fc 抑制体外人 CD4 T 细胞的激活，包括 IL-2 的分泌。总之，我们已经鉴定出一种在过敏反应中被调控的新型功能性 CDH，具有独特的免疫调节特性，因为它与α4 和 αE 整合素结合，并调节白细胞黏附和激活，因此可能代表通过 CDH26-Fc 进行免疫调节和治疗的新的检查点。
