Immune and non-immune functions of adipose tissue leukocytes

Trim, William; Lynch, Lydia

doi:10.1038/s41577-021-00635-7

Cited by 83 publications

(64 citation statements)

References 211 publications

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“…Congruent with this, an immune-dependent component is also involved in the control of hepatic insulin sensitivity [63]. These finely-tuned immunometabolic processes are impaired during obesity, where a Th1 immune environment is believed to contribute to local low-grade inflammation and metabolic dysfunctions [64; 65]. Since we showed that fh FABP1 induced changes in the Th2/Th1 balance, both in vitro and in vivo , we investigated whether repeated administration of the recombinant molecule could improve metabolic homeostasis in obesity-induced insulin-resistant mice.…”

Section: Discussionmentioning

confidence: 99%

Fasciola hepatica Fatty Acid Binding Protein 1 modulates T cell polarization by promoting dendritic cell thrombospondin-1 secretion without affecting metabolic homeostasis in obese mice

Zawistowska-Deniziak

Lambooij

Patente

et al. 2022

Preprint

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Background: The parasitic trematode Fasciola hepatica evades host immune defenses through secretion of various immunomodulatory molecules. Fatty Acid Binding Proteins (fhFABPs) are among the main excreted/secreted proteins and have been shown to display anti-inflammatory properties. However, little is currently known regarding their impact on dendritic cells (DCs) and their subsequent capacity to prime specific CD4+ T cell subsets. Methodology/Principal Findings: The immunomodulatory effects of both native F. hepatica extracts and recombinant fhFABPs were assessed on monocyte-derived human DCs (moDCs) and the underlying mechanism was next investigated using various approaches, including DC-allogenic T cell co-culture and DC phenotyping through transcriptomic, proteomic and FACS analyses. We mainly showed that fhFABP1 induced a tolerogenic-like phenotype in LPS-stimulated moDCs characterized by a dose-dependent increase in the cell-surface tolerogenic marker CD103 and IL-10 secretion, while DC co-stimulatory markers were not affected. A significant decrease in secretion of the pro-inflammatory cytokines IL-12p70 and IL-6 was also observed. In addition, these effects were associated with an increase in both Th2-on-Th1 ratio and IL-10 secretion by CD4+ T cells following DC-T cell co-culture. RNA sequencing and targeted proteomic analyses identified thrombospondin-1 (TSP-1) as a non-canonical factor highly expressed and secreted by fhFABP1-primed moDCs. The effect of fhFABP1 on T cell skewing was abolished when using a TSP-1 blocking antibody during DC-T cell co-culture. Immunomodulation by helminth molecules has been linked to improved metabolic homeostasis during obesity. Although fhFABP1 injection in high-fat diet-fed obese mice induced a potent Th2 immune response in adipose tissue, it did not improved insulin sensitivity or glucose homeostasis. Conclusions/Significance: We show that fhFABP1 modulates T cell polarization, notably by promoting DC TSP-1 secretion in vitro, without affecting metabolic homeostasis in a mouse model of type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Fasciola hepatica Fatty Acid Binding Protein 1 modulates T cell polarization by promoting dendritic cell thrombospondin-1 secretion without affecting metabolic homeostasis in obese mice

Zawistowska-Deniziak

Lambooij

Patente

et al. 2022

Preprint

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“…There is emerging evidence regarding the non-canonical functions of AT immune cells beyond immune-modulation, including angiogenesis and browning/beiging [ 105 , 113–115 ]. In addition to their anti-inflammatory properties, the M2-like ATMs are activated during a cold challenge to secrete the signalling protein SLIT3, which promotes the AT sympathetic nerve fibres to release norepinephrine and to nudge the white adipocytes into thermogenic adipocytes [ 116 ].…”

Section: Reprogramming By Immune Modulationmentioning

confidence: 99%

The shades of grey in adipose tissue reprogramming

Hui

2022

Bioscience Reports

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The adipose tissue (AT) has a major role in contributing to obesity-related pathologies through regulating systemic immuno-metabolism. The pathogenicity of the AT is underpinned by its remarkable plasticity to be reprogrammed under the condition of obesity, in the perspectives of tissue morphology, extracellular matrix (ECM) composition, angiogenesis, immuno-metabolic homeostasis and circadian rhythmicity. Dysregulation in these features escalates the pathogenesis conferred by this endo-metabolic organ. Intriguingly, the potential to be reprogrammed appears to be an Achilles' heel of the obese AT that can be targeted for the management of obesity and its associated comorbidities. Here, we provide an overview of the reprogramming processes of white AT (WAT), with a focus on their dynamics and pleiotropic actions over local and systemic homeostasis, followed by a discussion of potential strategies favouring therapeutic reprogramming. The potential involvement of AT remodelling in the pathogenesis of COVID-19 is also summarized and discussed.

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“…They can increase the body’s energy expenditure and improve glucose and lipid metabolism, thus becoming promising targets for preventing and treating obesity and insulin resistance. Recently, Trim et al have reviewed that leukocytes in the adipose tissue regulate the homeostasis of adipocytes and respond to the changes of nutrition and body temperature ( 38 ). Here, we focus on the function of ILCs in the adipose tissue in both health and obese associated metabolic disease.…”

Section: Ilcs In Adipose Tissuementioning

confidence: 99%

Role of Innate lymphoid Cells in Obesity and Insulin Resistance

et al. 2022

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Obesity, a growing chronic metabolic disease, greatly increases the risk of metabolic syndrome which includes type 2 diabetes, fatty liver and cardiovascular diseases. Obesity-associated metabolic diseases significantly contribute to mortality and reduce life expectancy. Recently, innate lymphoid cells (ILCs) have emerged as crucial regulators of metabolic homeostasis and tissue inflammation. This review focuses on the roles of ILCs in different metabolic tissues, including adipose tissue, liver, pancreas, and intestine. We briefly outline the relationship between obesity, inflammation, and insulin resistance. We then discuss how ILCs in distinct metabolic organs may function to maintain metabolic homeostasis and contribute to obesity and its associated metabolic diseases. The potential of ILCs as the therapeutic target for obesity and insulin resistance is also addressed.

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Immune and non-immune functions of adipose tissue leukocytes

Cited by 83 publications

References 211 publications

Fasciola hepatica Fatty Acid Binding Protein 1 modulates T cell polarization by promoting dendritic cell thrombospondin-1 secretion without affecting metabolic homeostasis in obese mice

Fasciola hepatica Fatty Acid Binding Protein 1 modulates T cell polarization by promoting dendritic cell thrombospondin-1 secretion without affecting metabolic homeostasis in obese mice

The shades of grey in adipose tissue reprogramming

Role of Innate lymphoid Cells in Obesity and Insulin Resistance

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