T cell-derived IL-22 amplifies IL-1β-driven inflammation in human adipose tissue: relevance to obesity and type 2 diabetes.

  1. Michèle Guerre-Millo1,3,*
  1. 1INSERM, U872, Paris, F-75006 France; Université Pierre et Marie Curie-Paris6, Centre de Recherche des Cordeliers, UMR S 872, Paris, F-75006 France; Université Paris Descartes, UMR S 872, Paris, F-75006 France.
  2. 2Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition and Endocrinology Department, Paris, F-75013 France; CRNH-Ile de France, Paris, F-75013 France.
  3. 3Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, F-75013 France.
  1. Corresponding author: Michèle Guerre-Millo and Elise Dalmas E-mail: michele.guerre-millo{at}crc.jussieu.fr; elise.dalmas{at}unibas.ch

Abstract

Pro-inflammatory cytokines are critically involved in the alteration of adipose tissue biology leading to deterioration of glucose homeostasis in obesity. Here, we show a pronounced pro-inflammatory signature of adipose tissue macrophages in type 2 diabetic obese patients, mainly driven by increased NLRP3-dependent 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. Co-culture 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.

Footnotes

  • * Authors equally contributed

  • Received October 1, 2013.
  • Accepted January 29, 2014.

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