Author, as appears in the article.: Chang, Sook Kyung; Kohlgruber, Ayano C.; Mizoguchi, Fumitaka; Michelet, Xavier; Wolf, Benjamin J.; Wei, Kevin; Lee, Pui Y.; Lynch, Lydia; Duquette, Danielle; Ceperuelo-Mallafre, Victoria; Banks, Alexander S.; Brenner, Michael B.;
Department: Medicina i Cirurgia
URV's Author/s: Ceperuelo Mallafré, Maria Victoria
Keywords: T-cells Pulmonary-fibrosis Obesity Necrosis-factor-alpha Metabolic disease Lymph-nodes Insulin-resistance Homeostasis Expression Alternatively activated macrophages
Abstract: M2 macrophages, innate lymphoid type 2 cells (ILC2s), eosinophils, Tregs, and invariant NK T cells (iNKT cells) all help to control adipose tissue inflammation, while M1 macrophages, TNF, and other inflammatory cytokines drive inflammation and insulin resistance in obesity. Stromal cells regulate leukocyte responses in lymph nodes, but the role of stromal cells in adipose tissue inflammation is unknown. PDGFR alpha(+) stromal cells are major producers of IL-33 in adipose tissue. Here, we show that mesenchymal cadherin-11 modulates stromal fibroblast function. Cadherin-11-deficient mice displayed increased stromal production of IL-33, with concomitant enhancements in ILC2s and M2 macrophages that helped control adipose tissue inflammation. Higher expression levels of IL-33 in cadherin-11-deficient mice mediated ILC2 activation, resulting in higher IL-13 expression levels and M2 macrophage expansion in adipose tissue. Consistent with reduced adipose tissue inflammation, cadherin-11-deficient mice were protected from obesity-induced glucose intolerance and adipose tissue fibrosis. Importantly, anti-cadherin-11 mAb blockade similarly improved inflammation and glycemic control in obese WT mice. These results suggest that stromal fibroblasts expressing cadherin-11 regulate adipose tissue inflammation and thus highlight cadherin-11 as a potential therapeutic target for the management of obesity.
Thematic Areas: Saúde coletiva Odontología Medicine, research & experimental Medicine (miscellaneous) Medicine (all) Medicina veterinaria Medicina ii Medicina i Interdisciplinar General medicine Farmacia Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: victoria.ceperuelo@urv.cat
Author identifier: 0000-0002-4460-9761
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.jci.org/articles/view/86881
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Journal Of Clinical Investigation. 127 (9): 3306-3318
APA: Chang, Sook Kyung; Kohlgruber, Ayano C.; Mizoguchi, Fumitaka; Michelet, Xavier; Wolf, Benjamin J.; Wei, Kevin; Lee, Pui Y.; Lynch, Lydia; Duquette, Da (2017). Stromal cell cadherin-11 regulates adipose tissue inflammation and diabetes. Journal Of Clinical Investigation, 127(9), 3306-3318. DOI: 10.1172/JCI86881
Article's DOI: 10.1172/JCI86881
Entity: Universitat Rovira i Virgili
Journal publication year: 2017
Publication Type: Journal Publications