scholarly journals Alveolar macrophage transcriptomic profiling in COPD shows major lipid metabolism changes

2021 ◽  
pp. 00915-2020
Author(s):  
Wataru Fujii ◽  
Theodore S. Kapellos ◽  
Kevin Baßler ◽  
Kristian Händler ◽  
Lisa Holsten ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Immune Cells ◽  
Fatty Acid Biosynthesis ◽  
Immune Cell ◽  
Cholesterol Metabolism ◽  
Chronic Obstructive ◽  
Dependent Manner ◽  
Transcriptional Reprogramming ◽  
Copd Patients ◽  
Lipid Species

BackgroundImmune cells play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Albeit established changes in distribution and cellular functions of major immune cells, such as alveolar macrophages (AMs) and neutrophils, their transcriptional reprogramming and contribution to the pathophysiology of COPD are still not fully understood.Aim and methodsTo determine changes in transcriptional reprogramming and lipid metabolism in the major immune cell type within the bronchoalveolar lavage fluid, we analysed whole transcriptomes and lipidomes of sorted CD45+Lin−HLA-DR+CD66b−Autofluorescencehi AMs from control and COPD patients.ResultsWe observed global transcriptional reprogramming featuring a spectrum of activation states, including pro- and anti-inflammatory signatures. We further detected significant changes between COPD patients and controls in genes involved in lipid metabolism, such as fatty acid biosynthesis in GOLD2 patients. Based on these findings, assessment of a total of 202 lipid species in sorted AMs revealed changes of cholesteryl esters, monoacylglycerols and phospholipids in a disease grade-dependent manner.ConclusionsTranscriptome and lipidome profiling of COPD AMs revealed GOLD grade-dependent changes, such as in cholesterol metabolism and interferon alpha and gamma responses.

scholarly journals Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label

2018 ◽  
Vol 51 (1) ◽  
pp. 1701817 ◽  
Author(s):  
Rianne de Vries ◽  
Yennece W.F. Dagelet ◽  
Pien Spoor ◽  
Erik Snoey ◽  
Patrick M.C. Jak ◽  
...  
Keyword(s):  
Principal Component ◽  
Chronic Obstructive ◽  
Exhaled Breath ◽  
Dependent Manner ◽  
Cross Sectional ◽  
Exacerbation Rate ◽  
Copd Patients ◽  
Validation Set ◽  
Inflammatory Phenotypes ◽  
Chronic Airway

Asthma and chronic obstructive pulmonary disease (COPD) are complex and overlapping diseases that include inflammatory phenotypes. Novel anti-eosinophilic/anti-neutrophilic strategies demand rapid inflammatory phenotyping, which might be accessible from exhaled breath.Our objective was to capture clinical/inflammatory phenotypes in patients with chronic airway disease using an electronic nose (eNose) in a training and validation set.This was a multicentre cross-sectional study in which exhaled breath from asthma and COPD patients (n=435; training n=321 and validation n=114) was analysed using eNose technology. Data analysis involved signal processing and statistics based on principal component analysis followed by unsupervised cluster analysis and supervised linear regression.Clustering based on eNose resulted in five significant combined asthma and COPD clusters that differed regarding ethnicity (p=0.01), systemic eosinophilia (p=0.02) and neutrophilia (p=0.03), body mass index (p=0.04), exhaled nitric oxide fraction (p<0.01), atopy (p<0.01) and exacerbation rate (p<0.01). Significant regression models were found for the prediction of eosinophilic (R2=0.581) and neutrophilic (R2=0.409) blood counts based on eNose. Similar clusters and regression results were obtained in the validation set.Phenotyping a combined sample of asthma and COPD patients using eNose provides validated clusters that are not determined by diagnosis, but rather by clinical/inflammatory characteristics. eNose identified systemic neutrophilia and/or eosinophilia in a dose-dependent manner.

scholarly journals Supplementing Genistein for Breeder Hens Alters the Fatty Acid Metabolism and Growth Performance of Offsprings by Epigenetic Modification

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Zengpeng Lv ◽  
Hao Fan ◽  
Bochen Song ◽  
Guang Li ◽  
Dan Liu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Growth Performance ◽  
Fatty Acid Biosynthesis ◽  
Cholesterol Metabolism ◽  
Epigenetic Modification ◽  
Treated Group ◽  
Control Group ◽  
Histone H4 ◽  
Acyl Coenzyme A

The experiment was designed to clarify the effect and molecular mechanism of maternal genistein (GEN) on the lipid metabolism and developmental growth of offspring chicks. Laying broiler breeder (LBB) hens were supplemented with 40 mg/kg genistein (GEN), while the control group was fed with the low-soybean meal diet. The offspring chicks were grouped according to the mother generation with 8 replicates each. Hepatic transcriptome data revealed 3915 differentially expressed genes (DEGs, P adjusted < 0.05, fold change>1.5 or fold change<0.67) between chicks in the two groups. Maternal GEN activated the GH-IGF1-PI3K/Akt signaling pathway, which promoted the developmental processes and cellular amino acid metabolic processes, as well as inhibited the apoptotic process. GEN treatment significantly increased the weight gain, breast muscle percentage, and liver index in chicks. PANTHER clustering analysis suggested that maternal GEN enhanced the antioxidant activity of chicks by the upregulation of gene (SOD3, MT1, and MT4) expression. Accordingly, the activities of T-AOC and T-SOD in the liver were increased after GEN treatment. The overrepresentation tests revealed that maternal GEN influenced the glycolysis, unsaturated fatty acid biosynthesis, acyl-coenzyme A metabolism, lipid transport, and cholesterol metabolism in the chick livers. Hepatic cholesterol and long-chain fatty acid were significantly decreased after GEN treatment. However, the level of arachidonic acid was higher in the livers of the GEN-treated group compared with the CON group. Moreover, GEN treatment enhanced fatty acid β-oxidation and upregulated PPARδ expression in the chick liver. ChIP-qPCR analysis indicated that maternal GEN might induce histone H3-K36 trimethylation in the promoter region of PPARδ gene (PPARD) through Iws1, methyltransferases. It also induced histone H4-K12 acetylation at the PPARD promoter through MYST2, which activated the PPAR signaling pathways in the chick livers. In summary, supplementing LBB hens with GEN can alter lipid metabolism in the offspring chicks through epigenetic modification and improve the antioxidative capability as well as growth performance.

scholarly journals New Pharmacological Tools to Target Leukocyte Trafficking in Lung Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Kylie B. R. Belchamber ◽  
Michael J. Hughes ◽  
Daniella A. Spittle ◽  
Eloise M. Walker ◽  
Elizabeth Sapey
Keyword(s):  
Lung Disease ◽  
Immune Cells ◽  
Lung Diseases ◽  
Immune Cell ◽  
Current Evidence ◽  
Chronic Obstructive ◽  
Cellular Functions ◽  
Obstructive Pulmonary Disease ◽  
Microbial Invasion ◽  
Infection And Inflammation

Infection and inflammation of the lung results in the recruitment of non-resident immune cells, including neutrophils, eosinophils and monocytes. This swift response should ensure clearance of the threat and resolution of stimuli which drive inflammation. However, once the threat is subdued this influx of immune cells should be followed by clearance of recruited cells through apoptosis and subsequent efferocytosis, expectoration or retrograde migration back into the circulation. This cycle of cell recruitment, containment of threat and then clearance of immune cells and repair is held in exquisite balance to limit host damage. Advanced age is often associated with detrimental changes to the balance described above. Cellular functions are altered including a reduced ability to traffic accurately towards inflammation, a reduced ability to clear pathogens and sustained inflammation. These changes, seen with age, are heightened in lung disease, and most chronic and acute lung diseases are associated with an exaggerated influx of immune cells, such as neutrophils, to the airways as well as considerable inflammation. Indeed, across many lung diseases, pathogenesis and progression has been associated with the sustained presence of trafficking cells, with examples including chronic diseases such as Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis and acute infections such as Pneumonia and Pneumonitis. In these instances, there is evidence that dysfunctional and sustained recruitment of cells to the airways not only increases host damage but impairs the hosts ability to effectively respond to microbial invasion. Targeting leukocyte migration in these instances, to normalise cellular responses, has therapeutic promise. In this review we discuss the current evidence to support the trafficking cell as an immunotherapeutic target in lung disease, and which potential mechanisms or pathways have shown promise in early drug trials, with a focus on the neutrophil, as the quintessential trafficking immune cell.

scholarly journals Extracellular HMGB1 blockade inhibits tumor growth through profoundly remodeling immune microenvironment and enhances checkpoint inhibitor-based immunotherapy

2021 ◽  
Vol 9 (3) ◽  
pp. e001966
Author(s):  
Pascale Hubert ◽  
Patrick Roncarati ◽  
Stephanie Demoulin ◽  
Charlotte Pilard ◽  
Marie Ancion ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Advanced Glycation Endproducts ◽  
High Mobility ◽  
Suppressor Cells ◽  
Immune Checkpoint Blockade ◽  
Dependent Manner ◽  
Immune Microenvironment ◽  
Regulatory T Lymphocytes ◽  
Immune Checkpoint Blockade Antibodies

BackgroundHigh-mobility group box 1 (HMGB1) is a multifunctional redox-sensitive protein involved in various intracellular (eg, chromatin remodeling, transcription, autophagy) and extracellular (inflammation, autoimmunity) processes. Regarding its role in cancer development/progression, paradoxical results exist in the literature and it is still unclear whether HMGB1 mainly acts as an oncogene or a tumor suppressor.MethodsHMGB1 expression was first assessed in tissue specimens (n=359) of invasive breast, lung and cervical cancer and the two distinct staining patterns detected (nuclear vs cytoplasmic) were correlated to the secretion profile of malignant cells, patient outcomes and the presence of infiltrating immune cells within tumor microenvironment. Using several orthotopic, syngeneic mouse models of basal-like breast (4T1, 67NR and EpRas) or non-small cell lung (TC-1) cancer, the efficacy of several HMGB1 inhibitors alone and in combination with immune checkpoint blockade antibodies (anti-PD-1/PD-L1) was then investigated. Isolated from retrieved tumors, 14 immune cell (sub)populations as well as the activation status of antigen-presenting cells were extensively analyzed in each condition. Finally, the redox state of HMGB1 in tumor-extruded fluids and the influence of different forms (oxidized, reduced or disulfide) on both dendritic cell (DC) and plasmacytoid DC (pDC) activation were determined.ResultsAssociated with an unfavorable prognosis in human patients, we clearly demonstrated that targeting extracellular HMGB1 elicits a profound remodeling of tumor immune microenvironment for efficient cancer therapy. Indeed, without affecting the global number of (CD45+) immune cells, drastic reductions of monocytic/granulocytic myeloid-derived suppressor cells (MDSC) and regulatory T lymphocytes, a higher M1/M2 ratio of macrophages as well as an increased activation of both DC and pDC were continually observed following HMGB1 inhibition. Moreover, blocking HMGB1 improved the efficacy of anti-PD-1 cancer monoimmunotherapy. We also reported that a significant fraction of HMGB1 encountered within cancer microenvironment (interstitial fluids) is oxidized and, in opposite to its reduced isoform, oxidized HMGB1 acts as a tolerogenic signal in a receptor for advanced glycation endproducts-dependent manner.ConclusionCollectively, we present evidence that extracellular HMGB1 blockade may complement first-generation cancer immunotherapies by remobilizing antitumor immune response.

scholarly journals The role of oxidised self-lipids and alveolar macrophage CD1b expression in COPD

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miranda P. Ween ◽  
Jake B. White ◽  
Hai B. Tran ◽  
Violet Mukaro ◽  
Charles Jones ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Oxidation Products ◽  
Chronic Obstructive ◽  
Dependent Manner ◽  
Cell Toxicity ◽  
Phagocytic Capacity ◽  
Bronchial Epithelial ◽  
Copd Patients ◽  
Lipid Oxidation Products

AbstractIn chronic obstructive pulmonary disease (COPD) apoptotic bronchial epithelial cells are increased, and their phagocytosis by alveolar macrophages (AM) is decreased alongside bacterial phagocytosis. Epithelial cellular lipids, including those exposed on uncleared apoptotic bodies, can become oxidized, and may be recognized and presented as non-self by antigen presenting cells. CD1b is a lipid-presenting protein, previously only described in dendritic cells. We investigated whether CD1b is upregulated in COPD AM, and whether lipid oxidation products are found in the airways of cigarette smoke (CS) exposed mice. We also characterise CD1b for the first time in a range of macrophages and assess CD1b expression and phagocytic function in response to oxidised lipid. Bronchoalveolar lavage and exhaled breath condensate were collected from never-smoker, current-smoker, and COPD patients and AM CD1b expression and airway 8-isoprostane levels assessed. Malondialdehyde was measured in CS-exposed mouse airways by confocal/immunofluorescence. Oxidation of lipids produced from CS-exposed 16HBE14o- (HBE) bronchial epithelial cells was assessed by spectrophotometry and changes in lipid classes assessed by mass spectrometry. 16HBE cell toxicity was measured by flow cytometry as was phagocytosis, CD1b expression, HLA class I/II, and mannose receptor (MR) in monocyte derived macrophages (MDM). AM CD1b was significantly increased in COPD smokers (4.5 fold), COPD ex-smokers (4.3 fold), and smokers (3.9 fold), and AM CD1b significantly correlated with disease severity (FEV1) and smoking pack years. Airway 8-isoprostane also increased in smokers and COPD smokers and ex-smokers. Malondialdehyde was significantly increased in the bronchial epithelium of CS-exposed mice (MFI of 18.18 vs 23.50 for control). Oxidised lipid was produced from CS-exposed bronchial epithelial cells (9.8-fold of control) and showed a different overall lipid makeup to that of control total cellular lipid. This oxidised epithelial lipid significantly upregulated MDM CD1b, caused bronchial epithelial cell toxicity, and reduced MDM phagocytic capacity and MR in a dose dependent manner. Increased levels of oxidised lipids in the airways of COPD patients may be responsible for reduced phagocytosis and may become a self-antigen to be presented by CD1b on macrophages to perpetuate disease progression despite smoking cessation.

scholarly journals Identification of Molecular Mechanisms Underlying Sex-Associated Differences in the Chronic Obstructive Pulmonary Disease through Bioinformatics Analysis

2021 ◽  
Author(s):  
Fengshou Chen ◽  
Haijia Hou ◽  
Jie Han ◽  
Bing Tang
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Chronic Obstructive ◽  
Hub Genes ◽  
Obstructive Pulmonary Disease ◽  
P53 Signaling ◽  
Copd Patients ◽  
P53 Signaling Pathway

Abstract Background Accumulating evidence suggests the existence sex associated differences in the Chronic Obstructive Pulmonary Disease (COPD). However, limited knowledge exists on the molecular mechanisms underlying sex associated differences in COPD patients. Methods The GSE8581 dataset obtained from the GEO database was used to analyze differentially expressed genes (DEGs). Then enrichment analysis for DEGs were conducted through Metascape. PPI and the hub genes-pathway networks were constructed using the STRING database and Cytoscape software. Finally, the CTD was used to examine the relationships between the hub DEGs and COPD. Results The results revealed that different subsets of DEGs had different characteristics in GO functions and KEGG pathways. Different subsets of hub genes were obtained based on PPI network. The study then constructed the hub genes-pathway network for different subsets to explore the key signaling pathways and hub genes involved. The findings showed that NRAS and RAC1 functioned through “Rap1 signaling pathway” and “PI3K-Akt signaling pathway”, in male COPD patients. On the other hand, “Cholesterol metabolism” was among the important pathways in female COPD patients while the hub genes, APOE and APOC3 functioned through “Cholesterol metabolism”. Moreover, “Ubiquitin mediated proteolysis” and the “p53 signaling pathway” were shown to play more important roles in male COPD patients compared to their female counterparts. Furthermore, CDK2 and UBE2N were the hub genes involved in “p53 signaling pathway” and “Ubiquitin mediated proteolysis”, respectively. Finally the study identified the relationship between the hub genes and COPD in CTD. Conclusions The present study uncovered different molecular mechanisms in COPD patients based on sex. Additionally, distinct pathways and hub genes including NRAS, RAC1, APOE, APOC3, CDK2 and UBE2N were identified in the two genders of COPD patients. Further studies are needed to explore individualized treatment for COPD based on the findings.

scholarly journals Impact of Cholesterol Metabolism in Immune Cell Function and Atherosclerosis

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2021 ◽  
Author(s):  
María Aguilar-Ballester ◽  
Andrea Herrero-Cervera ◽  
Ángela Vinué ◽  
Sergio Martínez-Hervás ◽  
Herminia González-Navarro
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
De Novo ◽  
Cholesterol Metabolism ◽  
The Body ◽  
Cholesterol Homeostasis ◽  
Hematopoietic Stem ◽  
Regulatory Pathways ◽  
Cholesterol Levels ◽  
Atherosclerosis Development

Cholesterol, the most important sterol in mammals, helps maintain plasma membrane fluidity and is a precursor of bile acids, oxysterols, and steroid hormones. Cholesterol in the body is obtained from the diet or can be de novo synthetized. Cholesterol homeostasis is mainly regulated by the liver, where cholesterol is packed in lipoproteins for transport through a tightly regulated process. Changes in circulating lipoprotein cholesterol levels lead to atherosclerosis development, which is initiated by an accumulation of modified lipoproteins in the subendothelial space; this induces significant changes in immune cell differentiation and function. Beyond lesions, cholesterol levels also play important roles in immune cells such as monocyte priming, neutrophil activation, hematopoietic stem cell mobilization, and enhanced T cell production. In addition, changes in cholesterol intracellular metabolic enzymes or transporters in immune cells affect their signaling and phenotype differentiation, which can impact on atherosclerosis development. In this review, we describe the main regulatory pathways and mechanisms of cholesterol metabolism and how these affect immune cell generation, proliferation, activation, and signaling in the context of atherosclerosis.

scholarly journals Immune Cell Subtypes and Cytokines in Lung Tumor Microenvironment: Influence of COPD

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1217 ◽  
Author(s):  
Jun Tang ◽  
Daniel Ramis-Cabrer ◽  
Víctor Curull ◽  
Xuejie Wang ◽  
Liyun Qin ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Plasma Cells ◽  
Immune Cell ◽  
Lung Tumor ◽  
Tumor Resection ◽  
Chronic Obstructive ◽  
Igg Antibody ◽  
Immune Profile ◽  
Cell Counts ◽  
Copd Patients

Background: The immune microenvironment plays a role in tumorigenesis. Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for lung cancer (LC). We hypothesized that immune profile characterized by T regulatory (Treg), natural killer (NK), and plasma cells, as well as interleukin (IL)-10 and interferon-gamma, may differ within tumors of LC patients with/without COPD. Methods: Treg (anti-CD3 and anti-forkhead boxP3 antibodies), NK (anti-NCR1 antibody), IgG (anti-CD138-IgG antibody), IgA (anti-CD138-IgA antibody) using immunohistochemistry, and both IL-10 and interferon-gamma (ELISA) were quantified in tumor and non-tumor specimens (thoracotomy for lung tumor resection) from 33 LC–COPD patients and 20 LC-only patients. Results: Immune profile in tumor versus non-tumor specimens: Treg cell counts significantly increased in tumors of both LC and LC–COPD patients, while in tumors of the latter group, IgG-secreting plasma cells significantly decreased and IL-10 increased. No significant differences were seen in levels of NK cells, IgA-secreting cells, IgA/IgG, or interferon-gamma. Immune profile in tumors of LC–COPD versus LC: No significant differences were observed in tumors between LC–COPD and LC patients for any study marker. Conclusions: Immune cell subtypes and cytokines are differentially expressed in lung tumors, and the presence of COPD elicited a decline in IgG-secreting plasma cell levels but not in other cell types.

scholarly journals CTNNB1 Alternation Is a Potential Biomarker for Immunotherapy Prognosis in Patients With Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Lin Chen ◽  
Qiaodan Zhou ◽  
Junjie Liu ◽  
Wei Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Cholesterol Metabolism ◽  
Checkpoint Inhibitors ◽  
Treatment Plan ◽  
Gene Set Enrichment Analysis ◽  
Synonymous Mutations ◽  
Potential Biomarker

BackgroundThe emergence of immune checkpoint inhibitors (ICIs) marks the beginning of a new era of immunotherapy for hepatocellular carcinoma (HCC), however, not all patients respond successfully to this treatment. A major challenge for HCC immunotherapy is the development of ways to screen for those patients that would benefit from this type of treatment and determine the optimal treatment plan for individual patients. Therefore, it is important to find a biomarker which allows for the stratification of HCC patients, which distinguishes responders from non-responders, thereby further improving the clinical benefits for those undergoing immunotherapy.MethodsWe used univariate and multivariate Cox risk proportional regression models to evaluate the relationship between non-synonymous mutations with a mutation frequency greater than 10%. We made a prognosis of an immunotherapy HCC cohort using mutation and prognosis data. An additional three HCC queues from the cbioportal webtool were used for further verification. The CIBERSORT, IPS, quanTIseq, and MCPcounter algorithms were used to evaluate the immune cells. PCA and z-score algorithm were used to calculate immune-related signature with published gene sets. Gene set enrichment analysis (GSEA) was used to compare the differences in the pathway-based enrichment scores of candidate genes between mutant and wild types.ResultsUnivariate and multivariate Cox results showed that only CTNNB1-Mutant(CTNNB1-MUT) was associated with progression-free survival (PFS) of HCC patients in the immunotherapy cohort. After excluding the potential bias introduced by other clinical features, it was found that CTNNB1-MUT served as an independent predictor of the prognosis of HCC patients after immunotherapy (P &lt; 0.05; HR &gt; 1). The results of the tumor immune microenvironment (TIME) analysis showed that patients with CTNNB1-MUT had significantly reduced activated immune cells [such as T cells, B cells, M1-type macrophages, and dendritic cells (DCs)], significantly increased M2-type macrophages, a significantly decreased expression of immunostimulating molecules, low activity of the immune activation pathways (cytokine pathway, immune cell activation and recruitment) and highly active immune depletion pathways (fatty acid metabolism, cholesterol metabolism, and Wnt pathway).ConclusionsIn this study, we found CTNNB1-MUT to be a potential biomarker for HCC immunotherapy patients, because it identified those patients are less likely to benefit from ICIs.

Liver X receptors in immune cell function in humans

2015 ◽  
Vol 43 (4) ◽  
pp. 752-757 ◽  
Author(s):  
Kirsty E. Waddington ◽  
Elizabeth C. Jury ◽  
Inés Pineda-Torra
Keyword(s):  
Lipid Metabolism ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Cholesterol Homeostasis ◽  
Liver X Receptors ◽  
Inflammatory Stimuli ◽  
X Receptors ◽  
Species Specific

The liver X receptors (LXRs), LXRα and LXRβ, are transcription factors with well-established roles in the regulation of lipid metabolism and cholesterol homeostasis. In addition, LXRs influence innate and adaptive immunity, including responses to inflammatory stimuli, proliferation and differentiation, migration, apoptosis and survival. However, the majority of work describing the role of LXRs in immune cells has been carried out in mouse models, and there are a number of known species-specific differences concerning LXR function. Here we review what is known about the role of LXRs in human immune cells, demonstrating the importance of these receptors in the integration of lipid metabolism and immune function, but also highlighting the need for a better understanding of the species, isoform, and cell-type specific effects of LXR activation.

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