Nature communications · 2019
Leptin induces TNFα-dependent inflammation in acquired generalized lipodystrophy and combined Crohn's disease.
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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
Аннотация
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.