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Leptin induces TNFα-dependent inflammation in acquired generalized lipodystrophy and combined Crohn's disease.
Ziegler, Jörn F; Böttcher, Chotima; Letizia, Marilena; Yerinde, Cansu; Wu, Hao; Freise, Inka; Rodriguez-Sillke, Yasmina; Stoyanova, Ani K; Kreis, Martin E; Asbach, Patrick; Kunkel, Desiree; Priller, Josef; Anagnostopoulos, Ioannis; Kühl, Anja A; Miehle, Konstanze; Stumvoll, Michael; Tran, Florian; Fredrich, Broder; Forster, Michael; Franke, Andre; Bojarski, Christian; Glauben, Rainer; Löscher, Britt-Sabina; Siegmund, Britta; Weidinger, Carl.
Afiliación
  • Ziegler JF; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Böttcher C; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany.
  • Letizia M; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Yerinde C; Laboratory of Molecular Psychiatry and Department of Neuropsychiatry, Berlin, Germany.
  • Wu H; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Freise I; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany.
  • Rodriguez-Sillke Y; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Stoyanova AK; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany.
  • Kreis ME; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Asbach P; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany.
  • Kunkel D; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Priller J; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany.
  • Anagnostopoulos I; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Kühl AA; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany.
  • Miehle K; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Stumvoll M; Department of Visceral Surgery, Campus Benjamin Franklin, Berlin, Germany.
  • Tran F; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Fredrich B; Department of Visceral Surgery, Campus Benjamin Franklin, Berlin, Germany.
  • Forster M; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Franke A; Department of Radiology, Campus Benjamin Franklin, Berlin, Germany.
  • Bojarski C; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Glauben R; BIH Cytometry Core, Berlin Institute of Health, 10178, Berlin, Germany.
  • Löscher BS; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
  • Siegmund B; Laboratory of Molecular Psychiatry and Department of Neuropsychiatry, Berlin, Germany.
  • Weidinger C; BIH Berlin, DZNE Berlin and University of Edinburgh and UK DRI, Edinburgh, UK.
Nat Commun ; 10(1): 5629, 2019 12 10.
Article en En | MEDLINE | ID: mdl-31822667
ABSTRACT
Leptin has been shown to modulate intestinal inflammation in mice. However, clinical evidence regarding its immune-stimulatory potential in human Crohn's disease remains sparse. We here describe a patient with the unique combination of acquired generalized lipodystrophy and Crohn's disease (AGLCD) featuring a lack of adipose tissue, leptin deficiency and intestinal inflammation. Using mass and flow cytometry, immunohistochemistry and functional metabolic analyses, the AGLCD patient was compared to healthy individuals and Crohn's disease patients regarding immune cell composition, function and metabolism and the effects of recombinant N-methionylleptin (rLeptin) were evaluated. We provide evidence that rLeptin exerts diverse pro-inflammatory effects on immune cell differentiation and function, including the metabolic reprogramming of immune cells and the induction of TNFα, ultimately aggravating Crohn's disease in the AGLCD patient, which can be reversed by anti-TNFα therapy. Our results indicate that leptin is required for human immune homeostasis and contributes to autoimmunity in a TNFα-dependent manner.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leptina / Lipodistrofia Generalizada Congénita / Inflamación Límite: Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leptina / Lipodistrofia Generalizada Congénita / Inflamación Límite: Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Alemania