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- Title
T Cell–Derived IL-22 Amplifies IL-1β–Driven Inflammation in Human Adipose Tissue: Relevance to Obesity and Type 2 Diabetes.
- Authors
Dalmas, Elise; Venteclef, Nicolas; Caer, Charles; Poitou, Christine; Cremer, Isabelle; Aron-Wisnewsky, Judith; Lacroix-Desmazes, Sébastien; Bayry, Jagadeesh; Kaveri, Srinivas V.; Clément, Karine; André, Sébastien; Guerre-Millo, Michèle
- Abstract
Proinflammatory cytokines are critically involved in the alteration of adipose tissue biology leading to deterioration of glucose homeostasis in obesity. Here we show a pronounced proinflammatory signature of adipose tissue macrophages in type 2 diabetic obese patients, mainly driven by increased NLRP3-dependent interleukin (IL)-1β production. IL-1β release increased with glycemic deterioration and decreased after gastric bypass surgery. A specific enrichment of IL-17- and IL-22-producing CD4+ T cells was found in adipose tissue of type 2 diabetic obese patients. Coculture experiments identified the effect of macrophage-derived IL-1β to promote IL-22 and IL-17 production by human adipose tissue CD4+ T cells. Reciprocally, adipose tissue macrophages express IL-17 and IL-22 receptors, making them sensitive to IL-17 and IL-22. IL-22 increased IL-1β release by inducing pro-IL-1β transcription through activation of C-Jun pathways in macrophages. In sum, these human data identified IL-1β and the T-cell cytokine IL-22 as key players of a paracrine inflammatory pathway previously unidentified in adipose tissue, with a pathological relevance to obesity-induced type 2 diabetes. These results provide an additional rationale for targeting IL-1β in obesity-linked type 2 diabetes and may have important implications for the conception of novel combined anti-IL-1β and anti-IL-22 immunotherapy in human obesity.
- Publication
Diabetes, 2014, Vol 63, Issue 6, p1966
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db13-1511