Your browser doesn't support javascript.
loading
A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma.
Everman, Jamie L; Sajuthi, Satria P; Liegeois, Maude A; Jackson, Nathan D; Collet, Erik H; Peters, Michael C; Chioccioli, Maurizio; Moore, Camille M; Patel, Bhavika B; Dyjack, Nathan; Powell, Roger; Rios, Cydney; Montgomery, Michael T; Eng, Celeste; Elhawary, Jennifer R; Mak, Angel C Y; Hu, Donglei; Huntsman, Scott; Salazar, Sandra; Feriani, Luigi; Fairbanks-Mahnke, Ana; Zinnen, Gianna L; Michel, Cole R; Gomez, Joe; Zhang, Xing; Medina, Vivian; Chu, Hong Wei; Cicuta, Pietro; Gordon, Erin D; Zeitlin, Pamela; Ortega, Victor E; Reisdorph, Nichole; Dunican, Eleanor M; Tang, Monica; Elicker, Brett M; Henry, Travis S; Bleecker, Eugene R; Castro, Mario; Erzurum, Serpil C; Israel, Elliot; Levy, Bruce D; Mauger, David T; Meyers, Deborah A; Sumino, Kaharu; Gierada, David S; Hastie, Annette T; Moore, Wendy C; Denlinger, Loren C; Jarjour, Nizar N; Schiebler, Mark L.
Afiliação
  • Everman JL; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
  • Sajuthi SP; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
  • Liegeois MA; Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.
  • Jackson ND; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
  • Collet EH; Department of Cell and Developmental Biology, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.
  • Peters MC; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.
  • Chioccioli M; Department of Genetics and Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
  • Moore CM; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
  • Patel BB; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
  • Dyjack N; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
  • Powell R; Department of Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.
  • Rios C; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
  • Montgomery MT; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
  • Eng C; Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.
  • Elhawary JR; Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.
  • Mak ACY; Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.
  • Hu D; Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.
  • Huntsman S; Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.
  • Salazar S; Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.
  • Feriani L; Biological and Soft Systems Sector, Cavendish Laboratory, University of Cambridge, Cambridge, UK.
  • Fairbanks-Mahnke A; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
  • Zinnen GL; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
  • Michel CR; Department of Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.
  • Gomez J; Department of Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.
  • Zhang X; Department of Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.
  • Medina V; Centro de Neumología Pediatrica, San Juan, PR, USA.
  • Chu HW; Department of Medicine, National Jewish Health, Denver, CO, USA.
  • Cicuta P; Biological and Soft Systems Sector, Cavendish Laboratory, University of Cambridge, Cambridge, UK.
  • Gordon ED; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.
  • Zeitlin P; Department of Pediatrics, National Jewish Health, Denver, CO, USA.
  • Ortega VE; Mayo Clinic, Phoenix, AZ, USA.
  • Reisdorph N; Department of Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.
  • Dunican EM; School of Medicine, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland.
  • Tang M; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.
  • Elicker BM; University of California-San Francisco, San Francisco, CA, USA.
  • Henry TS; Duke University, Durham, NC, USA.
  • Bleecker ER; Department of Internal Medicine, Mayo Clinic, Phoenix, AZ, USA.
  • Castro M; University of Kansas Medical Center, Kansas City, KS, USA.
  • Erzurum SC; Cleveland Clinic, Cleveland, OH, USA.
  • Israel E; Harvard University, Cambridge, MA, USA.
  • Levy BD; Brigham and Women's Hospital and Harvard University, Cambridge, MA, USA.
  • Mauger DT; Pennsylvania State University, Hershey, PA, USA.
  • Meyers DA; Department of Internal Medicine, Mayo Clinic, Phoenix, AZ, USA.
  • Sumino K; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Gierada DS; Washington University, St. Louis, MO, USA.
  • Hastie AT; Wake Forest University School of Medicine, Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Winston Salem, NC, USA.
  • Moore WC; Wake Forest University School of Medicine, Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Winston Salem, NC, USA.
  • Denlinger LC; University of Wisconsin-Madison, Madison, WI, USA.
  • Jarjour NN; University of Wisconsin-Madison, Madison, WI, USA.
  • Schiebler ML; University of Wisconsin-Madison, Madison, WI, USA.
Nat Commun ; 15(1): 3900, 2024 May 09.
Article em En | MEDLINE | ID: mdl-38724552
ABSTRACT
By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Child / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Child / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article