Leptin induces TNFα-dependent inflammation in acquired generalized lipodystrophy and combined Crohn's disease.

Autor: Ziegler JF; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany., Böttcher C; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Laboratory of Molecular Psychiatry and Department of Neuropsychiatry, Berlin, Germany., Letizia M; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany., Yerinde C; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany., Wu H; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany., Freise I; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; 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.; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany., Stoyanova AK; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Department of Visceral Surgery, 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.; Department of Visceral Surgery, Campus Benjamin Franklin, Berlin, Germany., Asbach P; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Department of Radiology, 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.; BIH Cytometry Core, Berlin Institute of Health, 10178, Berlin, Germany., Priller J; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Laboratory of Molecular Psychiatry and Department of Neuropsychiatry, Berlin, Germany.; BIH Berlin, DZNE Berlin and University of Edinburgh and UK DRI, Edinburgh, UK., Anagnostopoulos I; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Department of Pathology, Campus Charité Mitte, Berlin, Germany., Kühl AA; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; iPATH.Berlin-Immunopathology for Experimental Models, Core Facility of the Charité, Berlin, Germany., Miehle K; Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany., Stumvoll M; Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany., Tran F; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany., Fredrich B; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany., Forster M; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany., Franke A; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany., Bojarski C; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany., Glauben R; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany., Löscher BS; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany., Siegmund B; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. britta.siegmund@charite.de.; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany. britta.siegmund@charite.de., Weidinger C; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. carl.weidinger@charite.de.; Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Berlin, Germany. carl.weidinger@charite.de.; Clinician Scientist Program, Berlin Institute of Health, Berlin, Germany. carl.weidinger@charite.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Dec 10; Vol. 10 (1), pp. 5629. Date of Electronic Publication: 2019 Dec 10.
DOI: 10.1038/s41467-019-13559-7
Abstrakt: 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.
Databáze: MEDLINE