An MHC II-Dependent Activation Loop between Adipose Tissue Macrophages and CD4+ T Cells Controls Obesity-Induced Inflammation

Cho, Kae Won; Morris, David L.; DelProposto, Jennifer B.; Geletka, Lynn M.; Zamarron, Brian F.; Martinez-Santibañez, Gabriel; Meyer, Kevin A.; Singer, Kanakadurga; O’Rourke, Robert W.; Lumeng, Carey N.

doi:10.1016/j.celrep.2014.09.004

Cited by 143 publications

(180 citation statements)

References 39 publications

(60 reference statements)

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“…MHC class II expression is induced on ATMs in eWAT during diet-induced obesity [3] and plays a pivotal role in regulating ATT numbers in mice [4]. Given our observations that CD40L stimulated H2-Ab1 and Cd86 expression in cultured ATMs (Fig.…”

Section: Cd40 Regulates Mhc Class II Expression On Atms During Hfd-inmentioning

confidence: 99%

“…Our group is interested in the nature and function of APCs in adipose tissue, and we have found that ATMs are the primary functional APC in fat that promote obesity-induced inflammation [3,4]. Here, we performed an independent evaluation of the importance of CD40 in obesity-induced metainflammation to determine whether CD40/CD0L signaling contributed to ATM-T cell cross talk in obese adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

“…Adipose tissue inflammation involves activation of both innate and adaptive immune responses [1,2]. MHC class II-restricted signals from macrophages and dendritic cells contribute to T cell activation in response to obesogenic cues and contribute to metabolic dysfunction [3][4][5]. ATMs and dendritic cells can function as APCs and provide critical cues to generate proinflammatory signals that include activation of adipose tissue CD4 + T cells toward a Th1 and effector/memory phenotype [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity

Morris

Oatmen

Mergian

et al. 2015

Journal of Leukocyte Biology

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Obesity activates both innate and adaptive immune responses in adipose tissue, but the mechanisms critical for regulating these responses remain unknown. CD40/CD40L signaling provides bidirectional costimulatory signals between antigen-presenting cells and CD4 + T cells, and CD40L expression is increased in obese humans. Therefore, we examined the contribution of CD40 to the progression of obesity-induced inflammation in mice. CD40 was highly expressed on adipose tissue macrophages in mice, and CD40/CD40L signaling promoted the expression of antigen-presenting cell markers in adipose tissue macrophages. When fed a high fat diet, Cd40-deficient mice had reduced accumulation of con- ) in lean and obese fat was similar between wildtype and knockout mice. Adipose tissue macrophage content and inflammatory gene expression in fat did not differ between obese wild-type and knockout mice; however, major histocompatibility complex class II and CD86 expression on adipose tissue macrophages was reduced in visceral fat from knockout mice. Similar results were observed in chimeric mice with hematopoietic Cd40-deficiency. Nonetheless, neither whole body nor hematopoietic disruption of CD40 ameliorated obesityinduced insulin resistance in mice. In human adipose tissue, CD40 expression was positively correlated with CD80 and CD86 expression in obese patients with type 2 diabetes. These findings indicate that CD40 signaling in adipose tissue macrophages regulates major histocompatibility complex class II and CD86 expression to control the expansion of CD4 + T cells; however, this is largely dispensable for the development of obesity-induced inflammation and insulin resistance in mice.

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Section: Cd40 Regulates Mhc Class II Expression On Atms During Hfd-inmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity

Morris

Oatmen

Mergian

et al. 2015

Journal of Leukocyte Biology

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“…7A and B). However, adipose macrophages, B cells, and dendritic cells as APCs derived from bone marrow infiltrate into adipose tissue under physiological and pathological conditions (28)(29)(30). The antigen-presenting function of these cells in the eWAT should be considered.…”

Section: Inhibition Of Adipocyte Mhcii Expression Mainly Mediates Thementioning

confidence: 99%

Adrenomedullin 2 Improves Early Obesity-Induced Adipose Insulin Resistance by Inhibiting the Class II MHC in Adipocytes

Zhang

et al. 2016

Diabetes

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MHC class II (MHCII) antigen presentation in adipocytes was reported to trigger early adipose inflammation and insulin resistance. However, the benefits of MHCII inhibition in adipocytes remain largely unknown. Here, we showed that human plasma polypeptide adrenomedullin 2 (ADM2) levels were negatively correlated with HOMA of insulin resistance in obese human. Adipose-specific human ADM2 transgenic (aADM2-tg) mice were generated. The aADM2-tg mice displayed improvements in high-fat diet-induced early adipose insulin resistance. This was associated with increased insulin signaling and decreased systemic inflammation. ADM2 dose-dependently inhibited CIITA-induced MHCII expression by increasing Blimp1 expression in a CRLR/RAMP1-cAMP-dependent manner in cultured adipocytes. Furthermore, ADM2 treatment restored the high-fat diet-induced early insulin resistance in adipose tissue, mainly via inhibition of adipocyte MHCII antigen presentation and CD4 + T-cell activation. This study demonstrates that ADM2 is a promising candidate for the treatment of early obesity-induced insulin resistance.

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“…Genes 3.41E-04 fatty acid metabolic process 6 GO:0005777 have low blood glucose, insulin and free fatty acid levels (Cho et al, 2014).…”

Section: Scd Acaca Fasn Cd74mentioning

confidence: 99%

Gene Expression Profiling of Broiler Liver under Cold Stress by High-Throughput Sequencing Technology

Liu

Lü

et al. 2017

J. Poult. Sci.

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Cold stress is a major environmental factor restricting the sustainable development of animal husbandry. To gain insight into the gene-regulation processes in broilers under cold stress, gene expression profiling was conducted using high-throughput Solexa sequencing of broiler liver tissue under cold stress conditions and control conditions. According to Solexa sequencing, we identified 255 genes whose expression levels differed between the treatment and control group. Under cold stress, 135 genes were up-regulated and 120 genes were down-regulated genes compared with levels in the control group. Moreover, 469 genes were expressed only in the control group, and 172 genes were expressed only in the treatment group. These data were confirmed by real-time quantitative PCR. Gene Ontology enrichment analysis showed that the differentially expressed genes (DEGs) were mainly enriched in material metabolism and immune functions. KEGG enrichment analysis showed that DEGs were enriched in pyruvate metabolism, glycolysis/gluconeogenesis, fatty acid metabolism，insulin signaling pathway and others. In conclusion, these results may serve as an important reference for broiler breeding and provide new clues for the elucidation of molecular mechanisms of cold stress.

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An MHC II-Dependent Activation Loop between Adipose Tissue Macrophages and CD4+ T Cells Controls Obesity-Induced Inflammation

Cited by 143 publications

References 39 publications

CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity

CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity

Adrenomedullin 2 Improves Early Obesity-Induced Adipose Insulin Resistance by Inhibiting the Class II MHC in Adipocytes

Gene Expression Profiling of Broiler Liver under Cold Stress by High-Throughput Sequencing Technology

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