Feasibility of quantifying change in immune white cells in abdominal adipose tissue in response to an immune modulator in clinical obesity

Sattler, Fred R.; Mert, Melissa; Sankaranarayanan, Ishwarya; Mack, Wendy J.; Galle-Treger, Lauriane; González, Evelyn; Baronikian, Lilit; Lee, Kyuwan; Jahani, Pedram Shafiei; Hodis, Howard N.; Dieli‐Conwright, Christina M.; Akbari, Omid

doi:10.1371/journal.pone.0237496

Cited by 4 publications

(4 citation statements)

References 56 publications

(84 reference statements)

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“…A few studies have reported that ARBs and DPP‐4 inhibitors reduce inflammation markers in individuals with type 1 diabetes or type 2 diabetes 2–4,8–10 . There were no clear reductions in any of the measured markers during treatment with these drugs in our study, although the decrease in IL‐18 and IP‐10 observed after 4 weeks of treatment with linagliptin was observed in a prior study with DPP‐4 inhibitors 10,30 . The contrasting findings may be attributable to the short treatment period in ROTATE or because we measured the biomarkers in the systemic circulation, which is not always a proper reflection of the inflammatory marker concentration within tissues or organs 31 .…”

Section: Discussioncontrasting

confidence: 75%

“…2-4,8-10 There were no clear reductions in any of the measured markers during treatment with these drugs in our study, although the decrease in IL-18 and IP-10 observed after 4 weeks of treatment with linagliptin was observed in a prior study with DPP-4 inhibitors. 10,30 The contrasting findings may be attributable to the short treatment period in ROTATE or because we measured the biomarkers in the systemic circulation, which is not always a proper reflection of the inflammatory marker concentration within tissues or organs. 31 Unfortunately, we were unable to assess changes of the inflammatory markers in urine because these data were not available.…”

Section: Discussionmentioning

confidence: 99%

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Effects of albuminuria‐lowering treatments on inflammation markers: A post hoc analysis from the ROTATE trials

Sen

Curovic

Jongs

et al. 2023

Diabetes Obesity Metabolism

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Inflammation plays an important role in the initiation and progression of kidney function decline in individuals with diabetes. 1 In experimental models of diabetes and chronic kidney disease (CKD), interventions with drugs commonly used to treat cardiovascular and kidney complications have shown anti-inflammatory effects, including angiotensin receptor blockers (ARBs), 2-4 sodium-glucose co-transporter-2 (SGLT2) inhibitors, 5-7 dipeptidyl peptidase-4 (DPP-4) inhibitors, 8-10 and Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors. 11,12 In clinical studies, treatment with renin-angiotensin-aldosterone-system inhibitors, SGLT2 inhibitors, DPP-4 inhibitors and JAK-STAT inhibitors has also been shown to exert anti-inflammatory effects. 5,6,11,[13][14][15][16] The follow-up of most previous studies was more than 6 months. It is therefore not clear if potential anti-inflammatory properties represent a direct anti-inflammatory effect or a secondary effect because of improved glycaemic control or preservation of kidney function. In addition, there are no clinical studies comparing head-tohead the anti-inflammatory properties of these agents. Accordingly, we analysed the data from two randomized crossover clinical studies, ROTATE-1 and ROTATE-2, to compare the anti-inflammatory effects of an ARB, SGLT2 inhibitor, DPP-4 inhibitor and JAK-STAT inhibitor in participants diagnosed with type 1 diabetes and type 2 diabetes. | METHODS | Patients and study designROTATE-1 and ROTATE-2 were randomized multicentre crossover trials to primarily determine the individual albuminuria-lowering response of the ARB, telmisartan, the SGLT2 inhibitor, empagliflozin, the DPP-4 inhibitor, linagliptin, and the JAK-STAT inhibitor, baricitinib, in participants with type 1 diabetes and type 2 diabetes,

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Section: Discussioncontrasting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Effects of albuminuria‐lowering treatments on inflammation markers: A post hoc analysis from the ROTATE trials

Sen

Curovic

Jongs

et al. 2023

Diabetes Obesity Metabolism

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“…The following established flow cytometric gating strategies based on previous publications [ 42 – 47 ] were used to quantify the different immune cell sub-populations using the eight-color BD FACSCANTO analyzer, and data were acquired using BD FACSDiva software (BD Bioscience, San Jose, CA): CD45+, CD14+, CD163- for M1 macrophages, CD45+, CD14+, CD163+ for M2 macrophages, CD45+, CD4+, CD25+, CD127 low for regulatory T cells (Treg), CD45+, CD4+, CD25+, CD127 high for T effector cells (Teff). The total number of M1, M2, Treg, Teff subsets were quantified using FlowJo version 10 software (TreeStar Ashland OR) and were normalized to grams of AT collected or per milliliter of blood collected, respectively, as previously described [ 44 , 47 – 49 ]. Gating strategy and flow cytometry of a representative sample are shown in Supplementary Fig.…”

Section: Methodsmentioning

confidence: 99%

Near-roadway air pollution, immune cells and adipokines among obese young adults

et al. 2022

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Background Air pollution has been associated with metabolic disease and obesity. Adipokines are potential mediators of these effects, but studies of air pollution-adipokine relationships are inconclusive. Macrophage and T cells in adipose tissue (AT) and blood modulate inflammation; however, the role of immune cells in air pollution-induced dysregulation of adipokines has not been studied. We examined the association between air pollution exposure and circulating and AT adipokine concentrations, and whether these relationships were modified by macrophage and T cell numbers in the blood and AT. Methods Fasting blood and abdominal subcutaneous AT biopsies were collected from 30 overweight/obese 18–26 year-old volunteers. Flow cytometry was used to quantify T effector (Teff, inflammatory) and regulatory (Treg, anti-inflammatory) lymphocytes and M1 [inflammatory] and M2 [anti-inflammatory]) macrophage cell number. Serum and AT leptin and adiponectin were measured using enzyme-linked immunosorbent assay (ELISA). Exposure to near-roadway air pollution (NRAP) from freeway and non-freeway vehicular sources and to regional particulate matter, nitrogen dioxide and ozone were estimated for the year prior to biopsy, based on participants’ residential addresses. Linear regression models were used to examine the association between air pollution exposures and adipokines and to evaluate effect modification by immune cell counts. Results An interquartile increase in non-freeway NRAP exposure during 1 year prior to biopsy was associated with higher leptin levels in both serum [31.7% (95% CI: 10.4, 52.9%)] and AT [19.4% (2.2, 36.6%)]. Non-freeway NRAP exposure effect estimates were greater among participants with greater than median Teff/Treg ratio and M1/M2 ratio in blood, and with greater M1 counts in AT. No adipokine associations with regional air pollutants were found. Discussion Our results suggest that NRAP may increase serum leptin levels in obese young adults, and this association may be promoted in a pro-inflammatory immune cell environment in blood and AT.

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“…Novel regulators of ILC2 function such as GITR ( 20 ) and DR3 ( 28 ) provide clear avenues for the amelioration of insulin resistance and establishing glucose tolerance in obese individuals. In vivo drug treatment has been shown to regulate human adipose ILC2 populations ( 198 ). Overall, more immunotherapeutic strategies need to be adapted to complex diseases such as T2DM as the presence of immune dysregulation is a key driver in their development and pathogenesis.…”

Section: Novel Targets For Amelioration Of T2dmmentioning

confidence: 99%

Type 2 Innate Lymphoid Cells: Protectors in Type 2 Diabetes

Painter

Akbari

2021

Front. Immunol.

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Type 2 innate lymphoid cells (ILC2) are the innate counterparts of Th2 cells and are critically involved in the maintenance of homeostasis in a variety of tissues. Instead of expressing specific antigen receptors, ILC2s respond to external stimuli such as alarmins released from damage. These cells help control the delicate balance of inflammation in adipose tissue, which is a determinant of metabolic outcome. ILC2s play a key role in the pathogenesis of type 2 diabetes mellitus (T2DM) through their protective effects on tissue homeostasis. A variety of crosstalk takes place between resident adipose cells and ILC2s, with each interaction playing a key role in controlling this balance. ILC2 effector function is associated with increased browning of adipose tissue and an anti-inflammatory immune profile. Trafficking and maintenance of ILC2 populations are critical for tissue homeostasis. The metabolic environment and energy source significantly affect the number and function of ILC2s in addition to affecting their interactions with resident cell types. How ILC2s react to changes in the metabolic environment is a clear determinant of the severity of disease. Treating sources of metabolic instability via critical immune cells provides a clear avenue for modulation of systemic homeostasis and new treatments of T2DM.

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Feasibility of quantifying change in immune white cells in abdominal adipose tissue in response to an immune modulator in clinical obesity

Cited by 4 publications

References 56 publications

Effects of albuminuria‐lowering treatments on inflammation markers: A post hoc analysis from the ROTATE trials

Effects of albuminuria‐lowering treatments on inflammation markers: A post hoc analysis from the ROTATE trials

Near-roadway air pollution, immune cells and adipokines among obese young adults

Type 2 Innate Lymphoid Cells: Protectors in Type 2 Diabetes

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