title: Cadherin 26 is an alpha integrin-binding epithelial receptor regulated during allergic inflammation.
abstract: 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.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Caldwell
authors.affiliation: Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Collins
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Kemme
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Sherrill
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wen
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rochman
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Stucke
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: L
authors.initials: L
authors.lastname: Amin
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tai
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Putnam
authors.affiliation: Department of Biological Chemistry, John Innes Centre, The Sainsbury Laboratory, Norwich, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Jiménez-Dalmaroni
authors.affiliation: The Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Wormald
authors.affiliation: Center for Autoimmune Genomics and Etiology, Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: A
authors.initials: A
authors.lastname: Porollo
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Abonia
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002648:Child; D002675:Child, Preschool; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007223:Infant; D007249:Inflammation / Q000276:immunology*; D039001:Integrin alpha Chains / Q000378:metabolism; D039441:Integrin alpha4 / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D011485:Protein Binding; D055815:Young Adult
chemical_list: C000627409:CDH26 protein, human; D015820:Cadherins; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; C091368:integrin beta7; D039441:Integrin alpha4