Body mass index affects the association between plasma lipids and peripheral eosinophils in a general chinese population: a cross-sectional survey.

BACKGROUND: Lipid metabolism affects type 2 immunity; however, the association between plasma lipids and eosinophilic inflammation in humans is uncertain. This study analysed the relationship between plasma lipids and peripheral eosinophils and whether patterns differ with different body mass indexes (BMI). METHODS: A cross-sectional survey including 62,441 healthy participants recruited from a regular health screening programme was conducted. Participants were divided into normal weight, overweight and obese subgroups according to BMI. RESULTS: Multiple linear regression analysis revealed that elevated logarithmic-transformed eosinophil counts (log(EOS)) significantly correlated with high total cholesterol(TC), triglyceride(TG), low-density lipoprotein-cholesterol (LDL-C), and low high-density lipoprotein-cholesterol (HDL-C)levels in the overall population, as well as in men and women, while certain associations between peripheral blood eosinophil percentage and serum lipids varied by gender. These correlations existed across almost all BMI subgroups, and standardised ß values decreased sequentially with increasing BMI. HDL-C had the most significant effect on eosinophils in obese women. Two-factor analysis of variance showed log(EOS) increased with higher BMI and hyperlipidemia whether in male or female and a synergistic effect exists of lipid levels (TG and LDL-C) and BMI in men. CONCLUSIONS: Blood eosinophil counts were correlated with blood lipid levels and modified by body mass index status. The effects of lipid levels and body mass index on blood eosinophil counts were synergistic. Therefore, lipid metabolism may be involved in systemic eosinophil inflammation.

Impact of Lipid Metabolism on Macrophage Polarization: Implications for Inflammation and Tumor Immunity.

Macrophage polarization is influenced by lipids, which also exert significant control over macrophage functions. Lipids and their metabolites are players in intricate signaling pathways that modulate macrophages' responses to pathogens, phagocytosis, ferroptosis, and inflammation. This review focuses on lipid metabolism and macrophage functions and addresses potential molecular targets for the treatment of macrophage-related diseases. While lipogenesis is crucial for lipid accumulation and phagocytosis in M1 macrophages, M2 macrophages likely rely on fatty acid ß-oxidation to utilize fatty acids as their primary energy source. Cholesterol metabolism, regulated by factors such as SREBPs, PPARs, and LXRs, is associated with the cholesterol efflux capacity and the formation of foam cells (M2-like macrophages). Foam cells, which are targets for atherosclerosis, are associated with an increase in inflammatory cytokines. Lipolysis and fatty acid uptake markers, such as CD36, also contribute to the production of cytokines. Enhancing the immune system through the inhibition of lipid-metabolism-related factors can potentially serve as a targeted approach against tumor cells. Cyclooxygenase inhibitors, which block the conversion of arachidonic acid into various inflammatory mediators, influence macrophage polarization and have generated attention in cancer research.

Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling multisystem illness in which individuals are plagued with fatigue, inflammatory symptoms, cognitive dysfunction, and the hallmark symptom, post-exertional malaise. While the cause of this disease remains unknown, there is evidence of a potential infectious component that, along with patient symptoms and common onsets of the disease, implicates immune system dysfunction. To further our understanding of the state of ME/CFS lymphocytes, we characterized the role of fatty acids in isolated Natural Killer cells, CD4+ T cells, and CD8+ T cells in circulation and after overnight stimulation, through implicit perturbations to fatty acid oxidation. We examined samples obtained from at least 8 and as many as 20 subjects for immune cell fatty acid characterization in a variety of experiments and found that all three isolated cell types increased their utilization of lipids and levels of pertinent proteins involved in this metabolic pathway in ME/CFS samples, particularly during higher energy demands and activation. In T cells, we characterized the cell populations contributing to these metabolic shifts, which included CD4+ memory cells, CD4+ effector cells, CD8+ naïve cells, and CD8+ memory cells. We also discovered that patients with ME/CFS and healthy control samples had significant correlations between measurements of CD4+ T cell fatty acid metabolism and demographic data. These findings provide support for metabolic dysfunction in ME/CFS immune cells. We further hypothesize about the consequences that these altered fuel dependencies may have on T and NK cell effector function, which may shed light on the illness's mechanism of action.

Involvement of Fatty Acids and Their Metabolites in the Development of Inflammation in Atherosclerosis.

Despite all the advances of modern medicine, atherosclerosis continues to be one of the most important medical and social problems. Atherosclerosis is the cause of several cardiovascular diseases, which are associated with high rates of disability and mortality. The development of atherosclerosis is associated with the accumulation of lipids in the arterial intima and the disruption of mechanisms that maintain the balance between the development and resolution of inflammation. Fatty acids are involved in many mechanisms of inflammation development and maintenance. Endothelial cells demonstrate multiple cross-linkages between lipid metabolism and innate immunity. In addition, these processes are linked to hemodynamics and the function of other cells in the vascular wall, highlighting the central role of the endothelium in vascular biology.

Restriction of extracellular lipids renders pancreatic cancer dependent on autophagy.

BACKGROUND: KRAS is the predominant oncogene mutated in pancreatic ductal adenocarcinoma (PDAC), the fourth cause of cancer-related deaths worldwide. Mutant KRAS-driven tumors are metabolically programmed to support their growth and survival, which can be used to identify metabolic vulnerabilities. In the present study, we aimed to understand the role of extracellularly derived fatty acids in KRAS-driven pancreatic cancer. METHODS: To assess the dependence of PDAC cells on extracellular fatty acids we employed delipidated serum or RNAi-mediated suppression of ACSL3 (to inhibit the activation and cellular retention of extracellular fatty acids) followed by cell proliferation assays, qPCR, apoptosis assays, immunoblots and fluorescence microscopy experiments. To assess autophagy in vivo, we employed the KrasG12D/+;p53flox/flox;Pdx1-CreERT2 (KPC) mice crossed with Acsl3 knockout mice, and to assess the efficacy of the combination therapy of ACSL3 and autophagy inhibition we used xenografted human cancer cell-derived tumors in immunocompromised mice. RESULTS: Here we show that depletion of extracellularly derived lipids either by serum lipid restriction or suppression of ACSL3, triggers autophagy, a process that protects PDAC cells from the reduction of bioenergetic intermediates. Combined extracellular lipid deprivation and autophagy inhibition exhibits anti-proliferative and pro-apoptotic effects against PDAC cell lines in vitro and promotes suppression of xenografted human pancreatic cancer cell-derived tumors in mice. Therefore, we propose lipid deprivation and autophagy blockade as a potential co-targeting strategy for PDAC treatment. CONCLUSIONS: Our work unravels a central role of extracellular lipid supply in ensuring fatty acid provision in cancer cells, unmasking a previously unappreciated metabolic vulnerability of PDAC cells.

The interaction of secreted phospholipase A2-IIA with the microbiota alters its lipidome and promotes inflammation.

Secreted phospholipase A2-IIA (sPLA2-IIA) hydrolyzes phospholipids to liberate lysophospholipids and fatty acids. Given its poor activity toward eukaryotic cell membranes, its role in the generation of proinflammatory lipid mediators is unclear. Conversely, sPLA2-IIA efficiently hydrolyzes bacterial membranes. Here, we show that sPLA2-IIA affects the immune system by acting on the intestinal microbial flora. Using mice overexpressing transgene-driven human sPLA2-IIA, we found that the intestinal microbiota was critical for both induction of an immune phenotype and promotion of inflammatory arthritis. The expression of sPLA2-IIA led to alterations of the intestinal microbiota composition, but housing in a more stringent pathogen-free facility revealed that its expression could affect the immune system in the absence of changes to the composition of this flora. In contrast, untargeted lipidomic analysis focusing on bacteria-derived lipid mediators revealed that sPLA2-IIA could profoundly alter the fecal lipidome. The data suggest that a singular protein, sPLA2-IIA, produces systemic effects on the immune system through its activity on the microbiota and its lipidome.

Lipid metabolism in autoimmune rheumatic disease: implications for modern and conventional therapies.

Suppressing inflammation has been the primary focus of therapies in autoimmune rheumatic diseases (AIRDs), including rheumatoid arthritis and systemic lupus erythematosus. However, conventional therapies with low target specificity can have effects on cell metabolism that are less predictable. A key example is lipid metabolism; current therapies can improve or exacerbate dyslipidemia. Many conventional drugs also require in vivo metabolism for their conversion into therapeutically beneficial products; however, drug metabolism often involves the additional formation of toxic by-products, and rates of drug metabolism can be heterogeneous between patients. New therapeutic technologies and research have highlighted alternative metabolic pathways that can be more specifically targeted to reduce inflammation but also to prevent undesirable off-target metabolic consequences of conventional antiinflammatory therapies. This Review highlights the role of lipid metabolism in inflammation and in the mechanisms of action of AIRD therapeutics. Opportunities for cotherapies targeting lipid metabolism that could reduce immunometabolic complications and potential increased cardiovascular disease risk in patients with AIRDs are discussed.

Myeloid Cell-Derived Oxidized Lipids and Regulation of the Tumor Microenvironment.

Immunosuppressive myeloid cells play a major role in cancer by negatively regulating immune responses, promoting tumor progression, and limiting the efficacy of cancer immunotherapy. Immunosuppression is mediated by various mechanisms dependent upon the type of myeloid cell involved. In recent years, a more universal mechanism of immunosuppressive activity of myeloid cells has emerged: Generation of oxidized lipids. Oxidized lipids accumulate in all types of myeloid cells and are often transferred between cells. In this review, we discuss mechanisms involved in the generation and biological role of myeloid cell-derived oxidized lipids in cancer.

Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Recent experimental models and epidemiological studies suggest that specific environmental contaminants (ECs) contribute to the initiation and pathology of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms linking EC exposure with NAFLD remain poorly understood and there is no data on their impact on the human liver metabolome. Herein, we hypothesized that exposure to ECs, particularly perfluorinated alkyl substances (PFAS), impacts liver metabolism, specifically bile acid metabolism. METHODS: In a well-characterized human NAFLD cohort of 105 individuals, we investigated the effects of EC exposure on liver metabolism. We characterized the liver (via biopsy) and circulating metabolomes using 4 mass spectrometry-based analytical platforms, and measured PFAS and other ECs in serum. We subsequently compared these results with an exposure study in a PPARa-humanized mouse model. RESULTS: PFAS exposure appears associated with perturbation of key hepatic metabolic pathways previously found altered in NAFLD, particularly those related to bile acid and lipid metabolism. We identified stronger associations between the liver metabolome, chemical exposure and NAFLD-associated clinical variables (liver fat content, HOMA-IR), in females than males. Specifically, we observed PFAS-associated upregulation of bile acids, triacylglycerols and ceramides, and association between chemical exposure and dysregulated glucose metabolism in females. The murine exposure study further corroborated our findings, vis-à-vis a sex-specific association between PFAS exposure and NAFLD-associated lipid changes. CONCLUSIONS: Females may be more sensitive to the harmful impacts of PFAS. Lipid-related changes subsequent to PFAS exposure may be secondary to the interplay between PFAS and bile acid metabolism. LAY SUMMARY: There is increasing evidence that specific environmental contaminants, such as perfluorinated alkyl substances (PFAS), contribute to the progression of non-alcoholic fatty liver disease (NAFLD). However, it is poorly understood how these chemicals impact human liver metabolism. Here we show that human exposure to PFAS impacts metabolic processes associated with NAFLD, and that the effect is different in females and males.

Malondialdehyde-Acetaldehyde Modified (MAA) Proteins Differentially Effect the Inflammatory Response in Macrophage, Endothelial Cells and Animal Models of Cardiovascular Disease.

Chronic inflammation plays a critical role in the pathogenesis of atherosclerosis. Currently, the mechanism(s) by which inflammation contributes to this disease are not entirely understood. Inflammation is known to induce oxidative stress, which can lead to lipid peroxidation. Lipid peroxidation can result in the production of reactive by-products that can oxidatively modify macromolecules including DNA, proteins, and lipoproteins. A major reactive by-product of lipid peroxidation is malondialdehyde (MDA). MDA can subsequently break down to form acetaldehyde (AA). These two aldehydes can covalently interact with the epsilon (ε)-amino group of lysines within proteins and lipoproteins leading to the formation of extremely stable, highly immunogenic malondialdehyde/acetaldehyde adducts (MAA-adducts). The aim of this study was to investigate the inflammatory response to MAA-modified human serum albumin (HSA-MAA) and low-density lipoprotein (LDL-MAA). We found that animals injected with LDL-MAA generate antibodies specific to MAA-adducts. The level of anti-MAA antibodies were further increased in an animal model of atherosclerosis fed a Western diet. An animal model that combined both high fat diet and immunization of MAA-modified protein resulted in a dramatic increase in antibodies to MAA-adducts and vascular fat accumulation compared with controls. In vitro exposure of endothelial cells and macrophages to MAA-modified proteins resulted in increased fat accumulation as well as increased expression of adhesion molecules and pro-inflammatory cytokines. The expression of cytokines varied between the different cell lines and was unique to the individual modified proteins. The results of these studies demonstrate that different MAA-modified proteins elicit unique responses in different cell types. Additionally, the presence of MAA-modified proteins appears to modulate cellular metabolism leading to increased accumulation of triglycerides and further progression of the inflammatory response.

Mangiferin Ameliorates HFD-Induced NAFLD through Regulation of the AMPK and NLRP3 Inflammasome Signal Pathways.

Nonalcoholic fatty liver disease (NAFLD) is closely related to glycolipid metabolism and liver inflammation. And there is no effective drug approved for its clinical therapy. In this study, we focused on mangiferin (Man) and explored its effects and mechanisms on NAFLD treatment based on the regulation of glycolipid metabolism and anti-inflammatory in vivo and in vitro. The results exhibited that Man can significantly attenuate liver injury, insulin resistance, and glucose tolerance in high-fat diet- (HFD-) induced NAFLD mice and significantly reduce fat accumulation and inflammation in hepatic tissue of NAFLD mice. The transcriptome level RNA-seq analysis showed that the significantly different expression genes between the Man treatment group and the HFD-induced NAFLD model group were mainly related to regulation of energy, metabolism, and inflammation in liver tissue. Furthermore, western blots, real-time PCR, and immunohistochemistry experiments confirmed that Man significantly activated the AMPK signal pathway and inhibited NLRP3 inflammasome activation and pyroptosis in NAFLD mice. In in vitro cell experiments, we further confirmed that Man can promote glucose consumption and reduce intracellular triglyceride (TG) accumulation induced by free fatty acids in HepG2 cells and further that it can be blocked by AMPK-specific inhibitors. Western blot results showed that Man upregulated p-AMPKα levels and exhibited a significant AMPK activation effect, which was blocked by compound C. At the same time, Man downregulated the expression of NLRP3 inflammasome-related proteins and inhibited the activation of NLRP3 inflammasome, alleviating cell pyroptosis and inflammation effects. These results indicate that Man anti-NAFLD activity is mediated through its regulation of glucolipid metabolism by AMPK activation and its anti-inflammatory effects by NLRP3 inflammasome inhibition. Our study indicates that Man is a promising prodrug for the therapy of NAFLD patients.

ß2-adrenergic receptor signaling regulates metabolic pathways critical to myeloid-derived suppressor cell function within the TME.

Myeloid-derived suppressor cells (MDSCs) impede antitumor immunity; however, the precise mechanisms that regulate their suppressive function remain unresolved. Identifying these mechanisms could lead to therapeutic interventions to boost cancer immunotherapy efficacy. Here, we reveal that ß2 adrenergic receptor (ß2-AR) expression on MDSCs increases with tumor growth and that the ß2-AR stress pathway drives the immune suppressive activity of MDSCs by altering their metabolism. We show that ß2-AR signaling decreases glycolysis and increases oxidative phosphorylation and fatty acid oxidation (FAO). It also increases expression of the fatty acid transporter CPT1A, which is necessary for the FAO-mediated immunosuppressive function of MDSCs. Moreover, we show that ß2-AR signaling increases autophagy and activates the arachidonic acid cycle, both required for increasing the release of the immunosuppressive mediator, PGE2. Our data reveal that ß2-AR signaling triggered by stress is an important physiological regulator of key metabolic pathways in MDSCs, driving their immunosuppressive function.

Regulation of Sirt1 on energy metabolism and immune response in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease. Synovial hyperplasia and persistent inflammation serve as its typical pathological manifestations, which ultimately lead to joint destruction and function loss. Both clinical observations and metabolomics studies have revealed the prevalence of metabolic disorders in RA. In inflammatory immune microenvironments, energy metabolism is profoundly changed. Increasingly evidences suggest that this abnormality is involved in the occurrence and development of RA-related inflammation. Unsurprisingly, many energy metabolism sensors have been confirmed with immunoregulatory properties. As a representative, silent information regulator type 1 (Sirt1) controls many aspects of immune cells, such as cell lifespan, polarization, and secretion by functioning as a transcriptional regulator. Because of the profound clinical implication, researches on Sirt1 in the regulation of energy metabolism and immune functions under RA conditions have gradually gained momentum. This signaling balances glycolysis, lipid metabolism and insulin secretion orchestrating with other metabolism sensors, and consequently affects immune milieu through a so-called metabolism-immune feedback mechanism. This article reviews the involvement of Sirt1 in RA by discussing its impacts on energy metabolism and immune functions, and specially highlights the potential of Sirt1-targeting anti-rheumatic regimens. It also provides a theoretical basis for clarifying the mystery about the high incidence of metabolic complications in RA patients and identifying new anti-rheumatic reagents.

Anti-Inflammatory Effect of Muscle-Derived Interleukin-6 and Its Involvement in Lipid Metabolism.

Interleukin (IL)-6 has been studied since its discovery for its role in health and diseases. It is one of the most important pro-inflammatory cytokines. IL-6 was reported as an exacerbating factor in coronavirus disease. In recent years, it has become clear that the function of muscle-derived IL-6 is different from what has been reported so far. Exercise is accompanied by skeletal muscle contraction, during which, several bioactive substances, collectively named myokines, are secreted from the muscles. Many reports have shown that IL-6 is the most abundant myokine. Interestingly, it was indicated that IL-6 plays opposing roles as a myokine and as a pro-inflammatory cytokine. In this review, we discuss why IL-6 has different functions, the signaling mode of hyper-IL-6 via soluble IL-6 receptor (sIL-6R), and the involvement of soluble glycoprotein 130 in the suppressive effect of hyper-IL-6. Furthermore, the involvement of a disintegrin and metalloprotease family molecules in the secretion of sIL-6R is described. One of the functions of muscle-derived IL-6 is lipid metabolism in the liver. However, the differences between the functions of IL-6 as a pro-inflammatory cytokine and the functions of muscle-derived IL-6 are unclear. Although the involvement of myokines in lipid metabolism in adipocytes was previously discussed, little is known about the direct relationship between nonalcoholic fatty liver disease and muscle-derived IL-6. This review is the first to discuss the relationship between the function of IL-6 in diseases and the function of muscle-derived IL-6, focusing on IL-6 signaling and lipid metabolism in the liver.

Transcriptional Changes in Regulatory T Cells From Patients With Autoimmune Polyendocrine Syndrome Type 1 Suggest Functional Impairment of Lipid Metabolism and Gut Homing.

Autoimmune polyendocrine syndrome type I (APS-1) is a monogenic model disorder of organ-specific autoimmunity caused by mutations in the Autoimmune regulator (AIRE) gene. AIRE facilitates the expression of organ-specific transcripts in the thymus, which is essential for efficient removal of dangerous self-reacting T cells and for inducing regulatory T cells (Tregs). Although reduced numbers and function of Tregs have been reported in APS-I patients, the impact of AIRE deficiency on gene expression in these cells is unknown. Here, we report for the first time on global transcriptional patterns of isolated Tregs from APS-1 patients compared to healthy subjects. Overall, we found few differences between the groups, although deviant expression was observed for the genes TMEM39B, SKIDA1, TLN2, GPR15, FASN, BCAR1, HLA-DQA1, HLA-DQB1, HLA-DRA, GPSM3 and AKR1C3. Of significant interest, the consistent downregulation of GPR15 may indicate failure of Treg gut homing which could be of relevance for the gastrointestinal manifestations commonly seen in APS-1. Upregulated FASN expression in APS-1 Tregs points to increased metabolic activity suggesting a putative link to faulty Treg function. Functional studies are needed to determine the significance of these findings for the immunopathogenesis of APS-1 and for Treg immunobiology in general.

Peroxisome Deficiency Dysregulates Fatty Acid Oxidization and Exacerbates Lipotoxicity in ß Cells.

An adverse intrauterine environment impairs the development of pancreatic islets in the fetus and leads to insufficient ß cell mass and ß cell dysfunction. We previously reported that Pex14, a peroxin protein involved in the biogenesis and degradation of peroxisomes, is markedly reduced in the pancreas of an intrauterine growth restriction fetus and last into adulthood. Peroxisomes function in a wide range of metabolic processes including fatty acid oxidization, ROS detoxification, and anti-inflammatory responses. To elucidate the impact of downregulation of the Pex14 gene on ß cell, Pex14 was knocked down by siRNA in INS-1 cells. Pex14 knockdown disturbed peroxisomal biogenesis and dysregulated fatty acid metabolism and lipid storage capability, thereby increased ROS level and blunted insulin secretion. Moreover, Pex14 knockdown upregulated inflammation factors and regulators of endoplasmic reticulum stress. The lipotoxicity of fatty acid (including palmitic acid and linoleic acid) in ß cells was exacerbated by knockdown of Pex14, as indicated by H2O2 accumulation and increased programmed cell death. The present results demonstrate the vital role of Pex14 in maintaining normal peroxisome function and ß cell viability and highlight the importance of a functional peroxisomal metabolism for the detoxification of excess FAs in ß cells.

A lipidomic view of SARS-CoV-2.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which started in late 2019, has caused huge social and economic losses. A growing number of investigators are focusing on understanding the interaction of SARS-CoV-2 with host cellular processes to find therapeutic approaches. New data suggest that lipid metabolism may play a significant role in regulating the response of immune cells like macrophages to viral infection, thereby affecting the outcome of the disease. Therefore, understanding the role of lipid metabolism could help develop new therapeutic approaches to mitigate the social and economic cost of coronavirus disease 2019 (COVID-19).

ß-patchoulene protects against non-alcoholic steatohepatitis via interrupting the vicious circle among oxidative stress, histanoxia and lipid accumulation in rats.

Non-alcoholic steatohepatitis (NASH), an extreme progressive subtype of metabolic associated fatty liver disease, is well characterized by hepatic steatosis, injury and inflammation. It causes irreversible hepatic damage and there are no approved interventions for it. ß-PAE, a representatively pharmacological active substance isolated from Pogostemon cablin, has been indicated to alleviate hepatic steatosis and injury through modulating lipid metabolism in rats with simple steatosis. However, its protection against NASH remains unclear. Here, this study explored the potential effect of ß-PAE against high-fat diet-induced NASH in rats. The results displayed that ß-PAE significantly reduced the gains of body weight and epididymal adipose tissue, liver index and attenuated liver histological damages in NASH rats. It also markedly alleviated hepatic inflammation by inhibiting NLRP3 inflammasome activation. In NASH, the active NLRP3 inflammasome is caused by hepatic lipid abnormal accumulation-induced oxidative stress. Excessive oxidative stress results in hepatic histanoxia, which exacerbates lipid metabolism disorders by elevating CD36 to suppress AMPK signalling pathways. Moreover, the lipid accumulation led by lipid metabolism dysfunction intensifies oxidative stress. A vicious circle is formed among oxidative stress, histanoxia and lipid accumulation, eventually, but ß-PAE effectively interrupted it. Interestingly, soluble CD36 (sCD36) was tightly associated not only with hepatic steatosis and injury but also with inflammation. Collectively, ß-PAE exerted a positive effect against NASH by interrupting the vicious circle among oxidative stress, histanoxia and lipid accumulation, and sCD36 may be a promising non-invasive tool for NASH diagnosis.

Cholesterol metabolism: a new molecular switch to control inflammation.

The immune system protects the body against harm by inducing inflammation. During the immune response, cells of the immune system get activated, divided and differentiated in order to eliminate the danger signal. This process relies on the metabolic reprogramming of both catabolic and anabolic pathways not only to produce energy in the form of ATP but also to generate metabolites that exert key functions in controlling the response. Equally important to mounting an appropriate effector response is the process of immune resolution, as uncontrolled inflammation is implicated in the pathogenesis of many human diseases, including allergy, chronic inflammation and cancer. In this review, we aim to introduce the reader to the field of cholesterol immunometabolism and discuss how both metabolites arising from the pathway and cholesterol homeostasis are able to impact innate and adaptive immune cells, staging cholesterol homeostasis at the centre of an adequate immune response. We also review evidence that demonstrates the clear impact that cholesterol metabolism has in both the induction and the resolution of the inflammatory response. Finally, we propose that emerging data in this field not only increase our understanding of immunometabolism but also provide new tools for monitoring and intervening in human diseases, where controlling and/or modifying inflammation is desirable.