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Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis.
Moraes Holst, Luiza; Halfvarson, Jonas; Carlson, Marie; Hedin, Charlotte; Kruse, Robert; Lindqvist, Carl Mårten; Bergemalm, Daniel; Almér, Sven; Bresso, Francesca; Ling Lundström, Maria; Repsilber, Dirk; D'Amato, Mauro; Keita, Åsa; Hjortswang, Henrik; Söderholm, Johan; Sundin, Johanna; Törnblom, Hans; Simrén, Magnus; Strid, Hans; Magnusson, Maria K; Öhman, Lena.
Afiliación
  • Moraes Holst L; Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Halfvarson J; Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
  • Carlson M; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Hedin C; Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
  • Kruse R; Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
  • Lindqvist CM; School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
  • Bergemalm D; Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
  • Almér S; Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
  • Bresso F; Karolinska University Hospital, Gastroenterology Unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden.
  • Ling Lundström M; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Repsilber D; School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
  • D'Amato M; Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
  • Keita Å; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
  • Hjortswang H; Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain.
  • Söderholm J; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
  • Sundin J; Department of Clinical and Experimental Science, Linköping University, Linköping, Sweden.
  • Törnblom H; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
  • Simrén M; Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden.
  • Strid H; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Magnusson MK; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Öhman L; Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Clin Exp Gastroenterol ; 15: 129-144, 2022.
Article en En | MEDLINE | ID: mdl-35928254
Background: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn's disease (CD active). Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways. Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed. Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Clin Exp Gastroenterol Año: 2022 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Nueva Zelanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Clin Exp Gastroenterol Año: 2022 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Nueva Zelanda