Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance
Summary: Obesity modifies T cell populations in adipose tissue, thereby contributing to adipose tissue inflammation and insulin resistance. Here, we show that Rab4b, a small GTPase governing endocytic trafficking, is pivotal in T cells for the development of these pathological events. Rab4b expressi...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718318746 |
| _version_ | 1811267335536771072 |
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| author | Jérôme Gilleron Gwennaëlle Bouget Stoyan Ivanov Cindy Meziat Franck Ceppo Bastien Vergoni Mansour Djedaini Antoine Soprani Karine Dumas Arnaud Jacquel Laurent Yvan-Charvet Nicolas Venteclef Jean-François Tanti Mireille Cormont |
| author_facet | Jérôme Gilleron Gwennaëlle Bouget Stoyan Ivanov Cindy Meziat Franck Ceppo Bastien Vergoni Mansour Djedaini Antoine Soprani Karine Dumas Arnaud Jacquel Laurent Yvan-Charvet Nicolas Venteclef Jean-François Tanti Mireille Cormont |
| author_sort | Jérôme Gilleron |
| collection | DOAJ |
| description | Summary: Obesity modifies T cell populations in adipose tissue, thereby contributing to adipose tissue inflammation and insulin resistance. Here, we show that Rab4b, a small GTPase governing endocytic trafficking, is pivotal in T cells for the development of these pathological events. Rab4b expression is decreased in adipose T cells from mice and patients with obesity. The specific depletion of Rab4b in T cells causes adipocyte hypertrophy and insulin resistance in chow-fed mice and worsens insulin resistance in obese mice. This phenotype is driven by an increase in adipose Th17 and a decrease in adipose Treg due to a cell-autonomous skew of differentiation toward Th17. The Th17/Treg imbalance initiates adipose tissue inflammation and reduces adipogenesis, leading to lipid deposition in liver and muscles. Therefore, we propose that the obesity-induced loss of Rab4b in adipose T cells may contribute to maladaptive white adipose tissue remodeling and insulin resistance by altering adipose T cell fate. : Gilleron et al. show that Rab4b expression is decreased in adipose T cells during obesity in mice and humans. They reveal that Rab4b in T cells is critical for the control of adipose tissue remodeling and insulin sensitivity by regulating the adipose Th17/Treg balance. Keywords: immunometabolism, small GTPase, endocytosis, adipose tissue, ectopic lipids |
| first_indexed | 2024-04-12T20:59:29Z |
| format | Article |
| id | doaj.art-c2d16480a4704158978b3fd9e7d8c0ad |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T20:59:29Z |
| publishDate | 2018-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c2d16480a4704158978b3fd9e7d8c0ad2022-12-22T03:16:52ZengElsevierCell Reports2211-12472018-12-01251233293341.e5Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin ResistanceJérôme Gilleron0Gwennaëlle Bouget1Stoyan Ivanov2Cindy Meziat3Franck Ceppo4Bastien Vergoni5Mansour Djedaini6Antoine Soprani7Karine Dumas8Arnaud Jacquel9Laurent Yvan-Charvet10Nicolas Venteclef11Jean-François Tanti12Mireille Cormont13INSERM UMR1065, Mediterranean Center of Molecular Medicine C3M, Team “Cellular and Molecular Physiopathology of Obesity and Diabetes,” Nice, France; Université Côte d’Azur, Nice, FranceINSERM UMR1065, Mediterranean Center of Molecular Medicine C3M, Team “Cellular and Molecular Physiopathology of Obesity and Diabetes,” Nice, France; Université Côte d’Azur, Nice, FranceUniversité Côte d’Azur, Nice, France; INSERM U1065, Centre Méditerranéen de Médecine Moléculaire C3M, Team “Metabolism and Cancer,” Nice, FranceINSERM UMR1065, Mediterranean Center of Molecular Medicine C3M, Team “Cellular and Molecular Physiopathology of Obesity and Diabetes,” Nice, France; Université Côte d’Azur, Nice, FranceINSERM UMR1065, Mediterranean Center of Molecular Medicine C3M, Team “Cellular and Molecular Physiopathology of Obesity and Diabetes,” Nice, France; Université Côte d’Azur, Nice, FranceINSERM UMR1065, Mediterranean Center of Molecular Medicine C3M, Team “Cellular and Molecular Physiopathology of Obesity and Diabetes,” Nice, France; Université Côte d’Azur, Nice, FranceINSERM UMR1065, Mediterranean Center of Molecular Medicine C3M, Team “Cellular and Molecular Physiopathology of Obesity and Diabetes,” Nice, France; Université Côte d’Azur, Nice, FranceSorbonne Université, Université Pierre et Marie Curie, INSERM, UMR S_1138 Cordeliers Research Center, Paris, France; Clinique Geoffroy Saint-Hilaire, Ramsey Générale de Santé, Paris, FranceINSERM UMR1065, Mediterranean Center of Molecular Medicine C3M, Team “Cellular and Molecular Physiopathology of Obesity and Diabetes,” Nice, France; Université Côte d’Azur, Nice, FranceUniversité Côte d’Azur, Nice, France; INSERM U1065, Centre Méditerranéen de Médecine Moléculaire C3M, Team “Cell Death, Differentiation, and Cancer,” Nice, FranceUniversité Côte d’Azur, Nice, France; INSERM U1065, Centre Méditerranéen de Médecine Moléculaire C3M, Team “Metabolism and Cancer,” Nice, FranceSorbonne Université, Université Pierre et Marie Curie, INSERM, UMR S_1138 Cordeliers Research Center, Paris, FranceINSERM UMR1065, Mediterranean Center of Molecular Medicine C3M, Team “Cellular and Molecular Physiopathology of Obesity and Diabetes,” Nice, France; Université Côte d’Azur, Nice, FranceINSERM UMR1065, Mediterranean Center of Molecular Medicine C3M, Team “Cellular and Molecular Physiopathology of Obesity and Diabetes,” Nice, France; Université Côte d’Azur, Nice, France; Corresponding authorSummary: Obesity modifies T cell populations in adipose tissue, thereby contributing to adipose tissue inflammation and insulin resistance. Here, we show that Rab4b, a small GTPase governing endocytic trafficking, is pivotal in T cells for the development of these pathological events. Rab4b expression is decreased in adipose T cells from mice and patients with obesity. The specific depletion of Rab4b in T cells causes adipocyte hypertrophy and insulin resistance in chow-fed mice and worsens insulin resistance in obese mice. This phenotype is driven by an increase in adipose Th17 and a decrease in adipose Treg due to a cell-autonomous skew of differentiation toward Th17. The Th17/Treg imbalance initiates adipose tissue inflammation and reduces adipogenesis, leading to lipid deposition in liver and muscles. Therefore, we propose that the obesity-induced loss of Rab4b in adipose T cells may contribute to maladaptive white adipose tissue remodeling and insulin resistance by altering adipose T cell fate. : Gilleron et al. show that Rab4b expression is decreased in adipose T cells during obesity in mice and humans. They reveal that Rab4b in T cells is critical for the control of adipose tissue remodeling and insulin sensitivity by regulating the adipose Th17/Treg balance. Keywords: immunometabolism, small GTPase, endocytosis, adipose tissue, ectopic lipidshttp://www.sciencedirect.com/science/article/pii/S2211124718318746 |
| spellingShingle | Jérôme Gilleron Gwennaëlle Bouget Stoyan Ivanov Cindy Meziat Franck Ceppo Bastien Vergoni Mansour Djedaini Antoine Soprani Karine Dumas Arnaud Jacquel Laurent Yvan-Charvet Nicolas Venteclef Jean-François Tanti Mireille Cormont Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance Cell Reports |
| title | Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance |
| title_full | Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance |
| title_fullStr | Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance |
| title_full_unstemmed | Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance |
| title_short | Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance |
| title_sort | rab4b deficiency in t cells promotes adipose treg th17 imbalance adipose tissue dysfunction and insulin resistance |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718318746 |
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