title: T cell-derived IL-22 amplifies IL-1β-driven inflammation in human adipose tissue: relevance to obesity and type 2 diabetes.
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.
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, FranceInstitute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France michele.guerre-millo@crc.jussieu.fr elise.dalmas@unibas.ch.
authors: Elise
authors: E
authors: Dalmas
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, FranceInstitute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors: Nicolas
authors: N
authors: Venteclef
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, FranceInstitute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors: Charles
authors: C
authors: Caer
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, FranceInstitute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, FranceAssistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition and Endocrinology Department, Paris, France.
authors: Christine
authors: C
authors: Poitou
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, France.
authors: Isabelle
authors: I
authors: Cremer
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, FranceInstitute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, FranceAssistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition and Endocrinology Department, Paris, France.
authors: Judith
authors: J
authors: Aron-Wisnewsky
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, France.
authors: Sébastien
authors: S
authors: Lacroix-Desmazes
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, France.
authors: Jagadeesh
authors: J
authors: Bayry
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, France.
authors: Srinivas V
authors: SV
authors: Kaveri
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, FranceInstitute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, FranceAssistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition and Endocrinology Department, Paris, France.
authors: Karine
authors: K
authors: Clément
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, FranceInstitute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors: Sébastien
authors: S
authors: André
authors: INSERM, UMR-S 1166 and 1138, Paris, FranceSorbonne Universités, Pierre et Marie Curie-Paris6, Paris, FranceUniversité Paris Descartes, Paris, FranceInstitute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France michele.guerre-millo@crc.jussieu.fr elise.dalmas@unibas.ch.
authors: Michèle
authors: M
authors: Guerre-Millo
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D015153:Blotting, Western; D002460:Cell Line; D018920:Coculture Techniques; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D006442:Glycated Hemoglobin; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D007333:Insulin Resistance / Q000235:genetics; D053583:Interleukin-1beta / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D006442:Glycated Hemoglobin; D053583:Interleukin-1beta; D007378:Interleukins; D000097043:Interleukin-22; C517652:hemoglobin A1c protein, human