The Role of IL-13 and IL-4 in Adipose Tissue Fibrosis

• Published in: International journal of molecular sciences Vol. 24; no. 6; p. 5672
• Main Authors: Arndt, Lilli, Lindhorst, Andreas, Neugebauer, Julia, Hoffmann, Anne, Hobusch, Constance, Alexaki, Vasileia-Ismini, Ghosh, Adhideb, Blüher, Matthias, Wolfrum, Christian, Glaß, Markus, Gericke, Martin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Actin; Adipocytes; Adipose tissue; Adipose Tissue - pathology; Adipose Tissue, White - pathology; Adipose tissues; Analysis; Animals; B cells; Bisphosphonates; Body fat; Clodronic acid; Collagen; Correlation analysis; Cytokines; Depletion; Extracellular matrix; Fibroblasts; Fibronectin; Fibronectins; Fibrosis; Genetic aspects; Genotype & phenotype; Humans; IL-13; IL-4; Inflammation; Interleukin 13; Interleukin 4; Interleukin-13 - genetics; Interleukin-4 - genetics; Interleukins; Lipids; Macrophages; Metabolism; Mice; Obesity; Pathogenesis; Phenotypes; Scientific equipment and supplies industry; Smooth muscle; Type 2 diabetes; United States; Massachusetts; Germany; IL-4; adipose tissue; macrophages; fibrosis; IL-13; obesity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24065672

White adipose tissue (WAT) fibrosis, characterized by an excess of extracellular (ECM) matrix components, is strongly associated with WAT inflammation and dysfunction due to obesity. Interleukin (IL)-13 and IL-4 were recently identified as critical mediators in the pathogenesis of fibrotic diseases. However, their role in WAT fibrosis is still ill-defined. We therefore established an ex vivo WAT organotypic culture system and demonstrated an upregulation of fibrosis-related genes and an increase of α-smooth muscle actin (αSMA) and fibronectin abundance upon dose-dependent stimulation with IL-13/IL-4. These fibrotic effects were lost in WAT lacking , which encodes for the underlying receptor controlling this process. Adipose tissue macrophages were found to play a key role in mediating IL-13/IL-4 effects in WAT fibrosis as their depletion through clodronate dramatically decreased the fibrotic phenotype. IL-4-induced WAT fibrosis was partly confirmed in mice injected intraperitoneally with IL-4. Furthermore, gene correlation analyses of human WAT samples revealed a strong positive correlation of fibrosis markers with IL-13/IL-4 receptors, whereas and correlations failed to confirm this association. In conclusion, IL-13 and IL-4 can induce WAT fibrosis ex vivo and partly in vivo, but their role in human WAT remains to be further elucidated.