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Biology and function of adipose tissue macrophages, dendritic cells and B cells

      Highlights

      • Adipose tissue contains a large and diverse pattern of immune cells.
      • Adipose tissue macrophages play a critical role in the maintenance of adipose tissue homeostasis and obesity development.
      • Dendritic cells and B cells emerge as new players in adipose tissue control.

      Abstract

      The increasing incidence of obesity and its socio-economical impact is a global health issue due to its associated co-morbidities, namely diabetes and cardiovascular disease [
      • Flegal K.M.
      • Ogden C.L.
      Use of projection analyses and obesity trends-reply.
      ,
      • Ng M.
      • Fleming T.
      • Robinson M.
      • et al.
      Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.
      ,
      • Withrow D.
      • Alter D.A.
      The economic burden of obesity worldwide: a systematic review of the direct costs of obesity.
      ,
      • Tsai A.G.
      • Williamson D.F.
      • Glick H.A.
      Direct medical cost of overweight and obesity in the USA: a quantitative systematic review.
      ,
      • Wang Y.C.
      • McPherson K.
      • Marsh T.
      • et al.
      Health and economic burden of the projected obesity trends in the USA and the UK.
      ]. Obesity is characterized by an increase in adipose tissue, which promotes the recruitment of immune cells resulting in low-grade inflammation and dysfunctional metabolism. Macrophages are the most abundant immune cells in the adipose tissue of mice and humans. The adipose tissue also contains other myeloid cells (dendritic cells (DC) and neutrophils) and to a lesser extent lymphocyte populations, including T cells, B cells, Natural Killer (NK) and Natural Killer T (NKT) cells. While the majority of studies have linked adipose tissue macrophages (ATM) to the development of low-grade inflammation and co-morbidities associated with obesity, emerging evidence suggests for a role of other immune cells within the adipose tissue that may act in part by supporting macrophage homeostasis. In this review, we summarize the current knowledge of the functions ATMs, DCs and B cells possess during steady-state and obesity.

      Keywords

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      References

        • Flegal K.M.
        • Ogden C.L.
        Use of projection analyses and obesity trends-reply.
        J. Am. Med. Assoc. 2016; 316: 1317
        • Ng M.
        • Fleming T.
        • Robinson M.
        • et al.
        Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.
        Lancet. 2014; 384: 766-781
        • Withrow D.
        • Alter D.A.
        The economic burden of obesity worldwide: a systematic review of the direct costs of obesity.
        Obes. Rev. 2011; 12: 131-141
        • Tsai A.G.
        • Williamson D.F.
        • Glick H.A.
        Direct medical cost of overweight and obesity in the USA: a quantitative systematic review.
        Obes. Rev. 2011; 12: 50-61
        • Wang Y.C.
        • McPherson K.
        • Marsh T.
        • et al.
        Health and economic burden of the projected obesity trends in the USA and the UK.
        Lancet. 2011; 378: 815-825
        • Schulz C.
        • Gomez Perdiguero E.
        • Chorro L.
        • et al.
        A lineage of myeloid cells independent of Myb and hematopoietic stem cells.
        Science. 2012; 336: 86-90
        • Yona S.
        • Kim K.W.
        • Wolf Y.
        • et al.
        Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis.
        Immunity. 2013; 38: 79-91
        • Ginhoux F.
        • Greter M.
        • Leboeuf M.
        • et al.
        Fate mapping analysis reveals that adult microglia derive from primitive macrophages.
        Science. 2010; 330: 841-845
        • Epelman S.
        • Lavine K.J.
        • Beaudin A.E.
        • et al.
        Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation.
        Immunity. 2014; 40: 91-104
        • Hashimoto D.
        • Chow A.
        • Noizat C.
        • et al.
        Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes.
        Immunity. 2013; 38: 792-804
        • Jenkins S.J.
        • Ruckerl D.
        • Thomas G.D.
        • et al.
        IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1.
        J. Exp. Med. 2013; 210: 2477-2491
        • Bain C.C.
        • Hawley C.A.
        • Garner H.
        • et al.
        Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities.
        Nat. Commun. 2016; 7 (ncomms11852)
        • Scott C.L.
        • Zheng F.
        • De Baetselier P.
        • et al.
        Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells.
        Nat. Commun. 2016; 7: 10321
        • Hotamisligil G.S.
        • Shargill N.S.
        • Spiegelman B.M.
        Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.
        Science. 1993; 259: 87-91
        • Bornstein S.R.
        • Abu-Asab M.
        • Glasow A.
        • et al.
        Immunohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture.
        Diabetes. 2000; 49: 532-538
        • Weisberg S.P.
        • McCann D.
        • Desai M.
        • et al.
        Obesity is associated with macrophage accumulation in adipose tissue.
        J. Clin. Invest. 2003; 112: 1796-1808
        • Xu H.
        • Barnes G.T.
        • Yang Q.
        • et al.
        Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.
        J. Clin. Invest. 2003; 112: 1821-1830
        • Kintscher U.
        • Hartge M.
        • Hess K.
        • et al.
        T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance.
        Arterioscler. Thromb. Vasc. Biol. 2008; 28: 1304-1310
        • Wu H.
        • Ghosh S.
        • Perrard X.D.
        • et al.
        T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity.
        Circulation. 2007; 115: 1029-1038
        • Hassnain Waqas S.F.
        • Noble A.
        • Hoang A.C.
        • et al.
        Adipose tissue macrophages develop from bone marrow-independent progenitors in Xenopus laevis and mouse.
        J. Leukoc. Biol. 2017; 102: 845-855
        • Ampem G.
        • Azegrouz H.
        • Bacsadi A.
        • et al.
        Adipose tissue macrophages in non-rodent mammals: a comparative study.
        Cell Tissue Res. 2016; 363: 461-478
        • Osborn O.
        • Olefsky J.M.
        The cellular and signaling networks linking the immune system and metabolism in disease.
        Nat. Med. 2012; 18: 363-374
        • Chawla A.
        • Nguyen K.D.
        • Goh Y.P.
        Macrophage-mediated inflammation in metabolic disease.
        Nat. Rev. Immunol. 2011; 11: 738-749
        • Hassnain Waqas S.F.
        • Noble A.
        • Hoang A.C.
        • et al.
        Adipose tissue macrophages develop from bone marrow-independent progenitors in Xenopus laevis and mouse.
        J. Leukoc. Biol. 2017 Sep; 102: 845-855
        • Fan R.
        • Toubal A.
        • Goni S.
        • et al.
        Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes.
        Nat. Med. 2016; 22: 780-791
        • Leid J.
        • Carrelha J.
        • Boukarabila H.
        • et al.
        Primitive embryonic macrophages are required for coronary development and maturation.
        Circ. Res. 2016; 118: 1498-1511
        • Gautier E.L.
        • Shay T.
        • Miller J.
        • et al.
        Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages.
        Nat. Immunol. 2012; 13: 1118-1128
        • Miller J.C.
        • Brown B.D.
        • Shay T.
        • et al.
        Deciphering the transcriptional network of the dendritic cell lineage.
        Nat. Immunol. 2012; 13: 888-899
        • Lumeng C.N.
        • DelProposto J.B.
        • Westcott D.J.
        • et al.
        Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes.
        Diabetes. 2008; 57: 3239-3246
        • Xu X.
        • Grijalva A.
        • Skowronski A.
        • et al.
        Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation.
        Cell Metabol. 2013; 18: 816-830
        • Nagareddy P.R.
        • Kraakman M.
        • Masters S.L.
        • et al.
        Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.
        Cell Metabol. 2014; 19: 821-835
        • Ginhoux F.
        • Liu K.
        • Helft J.
        • et al.
        The origin and development of nonlymphoid tissue CD103+ DCs.
        J. Exp. Med. 2009; 206: 3115-3130
        • Cecchini M.G.
        • Dominguez M.G.
        • Mocci S.
        • et al.
        Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse.
        Development. 1994; 120: 1357-1372
        • Sugita S.
        • Kamei Y.
        • Oka J.
        • et al.
        Macrophage-colony stimulating factor in obese adipose tissue: studies with heterozygous op/+ mice.
        Obesity. 2007; 15: 1988-1995
        • Wang Y.
        • Szretter K.J.
        • Vermi W.
        • et al.
        IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia.
        Nat. Immunol. 2012; 13: 753-760
        • Greter M.
        • Lelios I.
        • Pelczar P.
        • et al.
        Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia.
        Immunity. 2012; 37: 1050-1060
        • Grayfer L.
        • Robert J.
        Distinct functional roles of amphibian (Xenopus laevis) colony-stimulating factor-1- and interleukin-34-derived macrophages.
        J. Leukoc. Biol. 2015; 98: 641-649
        • Chang E.J.
        • Lee S.K.
        • Song Y.S.
        • et al.
        IL-34 is associated with obesity, chronic inflammation, and insulin resistance.
        J. Clin. Endocrinol. Metab. 2014; 99: E1263-E1271
        • Zheng C.
        • Yang Q.
        • Cao J.
        • et al.
        Local proliferation initiates macrophage accumulation in adipose tissue during obesity.
        Cell Death Dis. 2016; 7 (e2167)
        • Serbina N.V.
        • Pamer E.G.
        Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2.
        Nat. Immunol. 2006; 7: 311-317
        • Amano S.U.
        • Cohen J.L.
        • Vangala P.
        • et al.
        Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation.
        Cell Metabol. 2014; 19: 162-171
        • Zheng C.
        • Yang Q.
        • Xu C.
        • et al.
        CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages.
        Proc. Natl. Acad. Sci. U. S. A. 2015; 112: E7239-E7248
        • Braune J.
        • Weyer U.
        • Hobusch C.
        • et al.
        IL-6 regulates M2 polarization and local proliferation of adipose tissue macrophages in obesity.
        J. Immunol. 2017; 198: 2927-2934
        • Waqas S.F.H.
        • Hoang A.C.
        • Lin Y.T.
        • et al.
        Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages.
        J. Clin. Invest. 2017 Sep 1; 127: 3559
        • Randolph G.J.
        Mechanisms that regulate macrophage burden in atherosclerosis.
        Circ. Res. 2014; 114: 1757-1771
        • Robbins C.S.
        • Hilgendorf I.
        • Weber G.F.
        • et al.
        Local proliferation dominates lesional macrophage accumulation in atherosclerosis.
        Nat. Med. 2013; 19: 1166-1172
        • Lumeng C.N.
        • Bodzin J.L.
        • Saltiel A.R.
        Obesity induces a phenotypic switch in adipose tissue macrophage polarization.
        J. Clin. Invest. 2007; 117: 175-184
        • Sun K.
        • Tordjman J.
        • Clement K.
        • et al.
        Fibrosis and adipose tissue dysfunction.
        Cell Metabol. 2013; 18: 470-477
        • Boulenouar S.
        • Michelet X.
        • Duquette D.
        • et al.
        Adipose type one innate lymphoid cells regulate macrophage homeostasis through targeted cytotoxicity.
        Immunity. 2017; 46: 273-286
        • Liang C.P.
        • Han S.
        • Okamoto H.
        • et al.
        Increased CD36 protein as a response to defective insulin signaling in macrophages.
        J. Clin. Invest. 2004; 113: 764-773
        • Han S.
        • Liang C.P.
        • DeVries-Seimon T.
        • et al.
        Macrophage insulin receptor deficiency increases ER stress-induced apoptosis and necrotic core formation in advanced atherosclerotic lesions.
        Cell Metabol. 2006; 3: 257-266
        • Tabas I.
        • Tall A.
        • Accili D.
        The impact of macrophage insulin resistance on advanced atherosclerotic plaque progression.
        Circ. Res. 2010; 106: 58-67
        • Rask-Madsen C.
        • Kahn C.R.
        Tissue-specific insulin signaling, metabolic syndrome, and cardiovascular disease.
        Arterioscler. Thromb. Vasc. Biol. 2012; 32: 2052-2059
        • Charo I.F.
        Macrophage polarization and insulin resistance: PPARgamma in control.
        Cell Metabol. 2007; 6: 96-98
        • Vergadi E.
        • Ieronymaki E.
        • Lyroni K.
        • et al.
        Akt signaling pathway in macrophage activation and m1/m2 polarization.
        J. Immunol. 2017; 198: 1006-1014
        • Spadaro O.
        • Camell C.D.
        • Bosurgi L.
        • et al.
        IGF1 shapes macrophage activation in response to immunometabolic challenge.
        Cell Rep. 2017; 19: 225-234
        • Lee Y.
        • Ka S.O.
        • Cha H.N.
        • et al.
        Myeloid Sirtuin 6 deficiency causes insulin resistance in high-fat diet-fed mice by eliciting macrophage polarization toward an M1 phenotype.
        Diabetes. 2017 Oct; 66: 2659-2668
        • Shan B.
        • Wang X.
        • Wu Y.
        • et al.
        The metabolic ER stress sensor IRE1alpha suppresses alternative activation of macrophages and impairs energy expenditure in obesity.
        Nat. Immunol. 2017; 18: 519-529
        • Huang S.C.
        • Everts B.
        • Ivanova Y.
        • et al.
        Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages.
        Nat. Immunol. 2014; 15: 846-855
        • Prieur X.
        • Mok C.Y.
        • Velagapudi V.R.
        • et al.
        Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice.
        Diabetes. 2011; 60: 797-809
        • Kaminski D.A.
        • Randall T.D.
        Adaptive immunity and adipose tissue biology.
        Trends Immunol. 2010; 31: 384-390
        • Mathis D.
        Immunological goings-on in visceral adipose tissue.
        Cell Metabol. 2013; 17: 851-859
        • Cancello R.
        • Henegar C.
        • Viguerie N.
        • et al.
        Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss.
        Diabetes. 2005; 54: 2277-2286
        • Boutens L.
        • Stienstra R.
        Adipose tissue macrophages: going off track during obesity.
        Diabetologia. 2016; 59: 879-894
        • Hill A.A.
        • Reid Bolus W.
        • Hasty A.H.
        A decade of progress in adipose tissue macrophage biology.
        Immunol. Rev. 2014; 262: 134-152
        • Olefsky J.M.
        • Glass C.K.
        Macrophages, inflammation, and insulin resistance.
        Annu. Rev. Physiol. 2010; 72: 219-246
        • Morris D.L.
        • Singer K.
        • Lumeng C.N.
        Adipose tissue macrophages: phenotypic plasticity and diversity in lean and obese states.
        Curr. Opin. Clin. Nutr. Metab. Care. 2011; 14: 341-346
        • Martinez-Santibanez G.
        • Lumeng C.N.
        Macrophages and the regulation of adipose tissue remodeling.
        Annu. Rev. Nutr. 2014; 34: 57-76
        • Chinetti-Gbaguidi G.
        • Staels B.
        Macrophage polarization in metabolic disorders: functions and regulation.
        Curr. Opin. Lipidol. 2011; 22: 365-372
        • Kraakman M.J.
        • Murphy A.J.
        • Jandeleit-Dahm K.
        • et al.
        Macrophage polarization in obesity and type 2 diabetes: weighing down our understanding of macrophage function?.
        Front. Immunol. 2014; 5: 470
        • Schipper H.S.
        • Nuboer R.
        • Prop S.
        • et al.
        Systemic inflammation in childhood obesity: circulating inflammatory mediators and activated CD14++ monocytes.
        Diabetologia. 2012; 55: 2800-2810
        • Murphy A.J.
        • Akhtari M.
        • Tolani S.
        • et al.
        ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice.
        J. Clin. Invest. 2011; 121: 4138-4149
        • Yvan-Charvet L.
        • Pagler T.
        • Gautier E.L.
        • et al.
        ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation.
        Science. 2010; 328: 1689-1693
        • Nasir K.
        • Guallar E.
        • Navas-Acien A.
        • et al.
        Relationship of monocyte count and peripheral arterial disease: results from the National Health and Nutrition Examination Survey 1999-2002.
        Arterioscler. Thromb. Vasc. Biol. 2005; 25: 1966-1971
        • Chapman C.M.
        • Beilby J.P.
        • McQuillan B.M.
        • et al.
        Monocyte count, but not C-reactive protein or interleukin-6, is an independent risk marker for subclinical carotid atherosclerosis.
        Stroke. 2004; 35: 1619-1624
        • Kanda H.
        • Tateya S.
        • Tamori Y.
        • et al.
        MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.
        J. Clin. Invest. 2006; 116: 1494-1505
        • Weisberg S.P.
        • Hunter D.
        • Huber R.
        • et al.
        CCR2 modulates inflammatory and metabolic effects of high-fat feeding.
        J. Clin. Invest. 2006; 116: 115-124
        • Reitman M.L.
        How does fat transition from white to beige?.
        Cell Metabol. 2017; 26: 14-16
        • Qiu Y.
        • Nguyen K.D.
        • Odegaard J.I.
        • et al.
        Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat.
        Cell. 2014; 157: 1292-1308
        • Rao R.R.
        • Long J.Z.
        • White J.P.
        • et al.
        Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis.
        Cell. 2014; 157: 1279-1291
        • Nguyen K.D.
        • Qiu Y.
        • Cui X.
        • et al.
        Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis.
        Nature. 2011; 480: 104-108
        • Fischer K.
        • Ruiz H.H.
        • Jhun K.
        • et al.
        Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.
        Nat. Med. 2017; 23: 623-630
        • Wolf Y.
        • Boura-Halfon S.
        • Cortese N.
        • et al.
        Brown-adipose-tissue macrophages control tissue innervation and homeostatic energy expenditure.
        Nat. Immunol. 2017; 18: 665-674
        • Camell C.D.
        • Sander J.
        • Spadaro O.
        • et al.
        Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing.
        Nature. 2017; 550: 119-123
        • Pirzgalska R.M.
        • Seixas E.
        • Seidman J.S.
        • et al.
        Sympathetic neuron-associated macrophages contribute to obesity by importing and metabolizing norepinephrine.
        Nat. Med. 2017; 23: 1309-1318
        • Chung K.J.
        • Chatzigeorgiou A.
        • Economopoulou M.
        • et al.
        A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity.
        Nat. Immunol. 2017; 18: 654-664
        • Steinman R.M.
        • Cohn Z.A.
        Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution.
        J. Exp. Med. 1973; 137: 1142-1162
        • Steinman R.M.
        • Cohn Z.A.
        Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro.
        J. Exp. Med. 1974; 139: 380-397
        • Steinman R.M.
        • Lustig D.S.
        • Cohn Z.A.
        Identification of a novel cell type in peripheral lymphoid organs of mice. 3. Functional properties in vivo.
        J. Exp. Med. 1974; 139: 1431-1445
        • Steinman R.M.
        • Witmer M.D.
        Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice.
        Proc. Natl. Acad. Sci. U. S. A. 1978; 75: 5132-5136
        • Swiecki M.
        • Colonna M.
        The multifaceted biology of plasmacytoid dendritic cells.
        Nat. Rev. Immunol. 2015; 15: 471-485
        • Forster R.
        • Schubel A.
        • Breitfeld D.
        • et al.
        CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs.
        Cell. 1999; 99: 23-33
        • Murphy T.L.
        • Grajales-Reyes G.E.
        • Wu X.
        • et al.
        Transcriptional control of dendritic cell development.
        Annu. Rev. Immunol. 2016; 34: 93-119
        • Bogunovic M.
        • Ginhoux F.
        • Helft J.
        • et al.
        Origin of the lamina propria dendritic cell network.
        Immunity. 2009; 31: 513-525
        • Varol C.
        • Vallon-Eberhard A.
        • Elinav E.
        • et al.
        Intestinal lamina propria dendritic cell subsets have different origin and functions.
        Immunity. 2009; 31: 502-512
        • Hildner K.
        • Edelson B.T.
        • Purtha W.E.
        • et al.
        Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity.
        Science. 2008; 322: 1097-1100
        • Hambleton S.
        • Salem S.
        • Bustamante J.
        • et al.
        IRF8 mutations and human dendritic-cell immunodeficiency.
        N. Engl. J. Med. 2011; 365: 127-138
        • Tailor P.
        • Tamura T.
        • Morse 3rd, H.C.
        • et al.
        The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse.
        Blood. 2008; 111: 1942-1945
        • Schlitzer A.
        • McGovern N.
        • Teo P.
        • et al.
        IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses.
        Immunity. 2013; 38: 970-983
        • Persson E.K.
        • Uronen-Hansson H.
        • Semmrich M.
        • et al.
        IRF4 transcription-factor-dependent CD103(+)CD11b(+) dendritic cells drive mucosal T helper 17 cell differentiation.
        Immunity. 2013; 38: 958-969
        • Williams J.W.
        • Tjota M.Y.
        • Clay B.S.
        • et al.
        Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation.
        Nat. Commun. 2013; 4: 2990
        • Vander Lugt B.
        • Khan A.A.
        • Hackney J.A.
        • et al.
        Transcriptional programming of dendritic cells for enhanced MHC class II antigen presentation.
        Nat. Immunol. 2014; 15: 161-167
        • Gao Y.
        • Nish S.A.
        • Jiang R.
        • et al.
        Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells.
        Immunity. 2013; 39: 722-732
        • Satpathy A.T.
        • Briseno C.G.
        • Lee J.S.
        • et al.
        Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens.
        Nat. Immunol. 2013; 14: 937-948
        • Tussiwand R.
        • Everts B.
        • Grajales-Reyes G.E.
        • et al.
        Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses.
        Immunity. 2015; 42: 916-928
        • Lewis K.L.
        • Caton M.L.
        • Bogunovic M.
        • et al.
        Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine.
        Immunity. 2011; 35: 780-791
        • Ivanov S.
        • Scallan J.P.
        • Kim K.W.
        • et al.
        CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability.
        J. Clin. Invest. 2016; 126: 1581-1591
        • Cho K.W.
        • Zamarron B.F.
        • Muir L.A.
        • et al.
        Adipose tissue dendritic cells are independent contributors to obesity-induced inflammation and insulin resistance.
        J. Immunol. 2016; 197: 3650-3661
        • Kuan E.L.
        • Ivanov S.
        • Bridenbaugh E.A.
        • et al.
        Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue dendritic cells.
        J. Immunol. 2015; 194: 5200-5210
        • Frikke-Schmidt H.
        • Zamarron B.F.
        • O'Rourke R.W.
        • et al.
        Weight loss independent changes in adipose tissue macrophage and T cell populations after sleeve gastrectomy in mice.
        Mol. Metabol. 2017; 6: 317-326
        • Hellmann J.
        • Sansbury B.E.
        • Holden C.R.
        • et al.
        CCR7 maintains nonresolving lymph node and adipose inflammation in obesity.
        Diabetes. 2016; 65: 2268-2281
        • Stefanovic-Racic M.
        • Yang X.
        • Turner M.S.
        • et al.
        Dendritic cells promote macrophage infiltration and comprise a substantial proportion of obesity-associated increases in CD11c+ cells in adipose tissue and liver.
        Diabetes. 2012; 61: 2330-2339
        • Bertola A.
        • Ciucci T.
        • Rousseau D.
        • et al.
        Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients.
        Diabetes. 2012; 61: 2238-2247
        • Chen Y.
        • Tian J.
        • Tian X.
        • et al.
        Adipose tissue dendritic cells enhances inflammation by prompting the generation of Th17 cells.
        PLoS One. 2014; 9 (e92450)
        • Ferris S.T.
        • Carrero J.A.
        • Mohan J.F.
        • et al.
        A minor subset of Batf3-dependent antigen-presenting cells in islets of Langerhans is essential for the development of autoimmune diabetes.
        Immunity. 2014; 41: 657-669
        • Shulzhenko N.
        • Morgun A.
        • Hsiao W.
        • et al.
        Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut.
        Nat. Med. 2011; 17: 1585-1593
        • Baumgarth N.
        B-1 cell heterogeneity and the regulation of natural and antigen-induced IgM production.
        Front. Immunol. 2016; 7: 324
        • Ying W.
        • Wollam J.
        • Ofrecio J.M.
        • et al.
        Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling.
        J. Clin. Invest. 2017; 127: 1019-1030
        • Winer D.A.
        • Winer S.
        • Shen L.
        • et al.
        B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies.
        Nat. Med. 2011; 17: 610-617
        • Nishimura S.
        • Manabe I.
        • Takaki S.
        • et al.
        Adipose natural regulatory B cells negatively control adipose tissue inflammation.
        Cell Metabol. 2013 Oct 22; (pii: S1550-4131(13)00386-0)
        • Zigmond E.
        • Bernshtein B.
        • Friedlander G.
        • et al.
        Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis.
        Immunity. 2014; 40: 720-733
        • Pasare C.
        • Medzhitov R.
        Control of B-cell responses by Toll-like receptors.
        Nature. 2005; 438: 364-368
        • van Beek L.
        • Vroegrijk I.O.
        • Katiraei S.
        • et al.
        FcRgamma-chain deficiency reduces the development of diet-induced obesity.
        Obesity. 2015; 23: 2435-2444
        • Bergtold A.
        • Desai D.D.
        • Gavhane A.
        • et al.
        Cell surface recycling of internalized antigen permits dendritic cell priming of B cells.
        Immunity. 2005; 23: 503-514
        • van Dam A.D.
        • van Beek L.
        • Pronk A.C.M.
        • et al.
        IgG is elevated in obese white adipose tissue but does not induce glucose intolerance via Fcgamma-receptor or complement.
        Int. J. Obes. (Lond). 2018 Feb; 42: 260-269
        • Harmon D.B.
        • Srikakulapu P.
        • Kaplan J.L.
        • et al.
        Protective role for B-1b B cells and IgM in obesity-associated inflammation, glucose intolerance, and insulin resistance.
        Arterioscler. Thromb. Vasc. Biol. 2016; 36: 682-691
        • Arai S.
        • Maehara N.
        • Iwamura Y.
        • et al.
        Obesity-associated autoantibody production requires AIM to retain the immunoglobulin M immune complex on follicular dendritic cells.
        Cell Rep. 2013; 3: 1187-1198
        • Kai T.
        • Yamazaki T.
        • Arai S.
        • et al.
        Stabilization and augmentation of circulating AIM in mice by synthesized IgM-Fc.
        PLoS One. 2014; 9e97037
        • Kurokawa J.
        • Arai S.
        • Nakashima K.
        • et al.
        Macrophage-derived AIM is endocytosed into adipocytes and decreases lipid droplets via inhibition of fatty acid synthase activity.
        Cell Metabol. 2010; 11: 479-492
        • Kyaw T.
        • Tay C.
        • Krishnamurthi S.
        • et al.
        B1a B lymphocytes are atheroprotective by secreting natural IgM that increases IgM deposits and reduces necrotic cores in atherosclerotic lesions.
        Circ. Res. 2011; 109: 830-840
        • Hosseini H.
        • Li Y.
        • Kanellakis P.
        • et al.
        Toll-like receptor (TLR)4 and MyD88 are essential for atheroprotection by peritoneal B1a B cells.
        J. Am. Heart Assoc. 2016; 5
        • Sage A.P.
        • Tsiantoulas D.
        • Baker L.
        • et al.
        BAFF receptor deficiency reduces the development of atherosclerosis in mice–brief report.
        Arterioscler. Thromb. Vasc. Biol. 2012; 32: 1573-1576