82 research outputs found
CD8+ T cells specific to apoptosis-associated epitopes are expanded in patients with chronic HBV infection and fibrosis
No full textBACKGROUND & AIMS: During chronic viral infections, the apoptosis of activated T cell elicits a CD8+ T cell response directed to those cryptic epitopes that emerge from caspase-cleaved structural proteins. Such response directed to apoptosis-associated epitopes (AE) contributes to the amplification of immunopathology.METHODS: Here, we have analysed through flow cytometry AE-specific CD8+ T cells in patients with chronic hepatitis B virus (HBV) infection, naive-to-treatment or undergoing nucleos(t)ide-analogue (NUC) therapy.RESULTS: We found that AE-specific CD8+ T cell frequencies were significantly increased only in those NUC-treated patients who also presented advanced hepatic fibrosis. Regulatory T cells were also expanded in those patients, and AE-specific, but not HBV-specific, CD8+ T cell frequency positively correlated with Treg percentages. Through multiparameter flow cytometry, multidimensionality reduction and unsupervised clustering analysis, we could identify novel subpopulations among effector memory (em) and emCD45RA+ T cell (Tem and Temra) subsets. CD8+ T cells with distinct specificities differentially populated the subpopulation map: while HBV-specific were mostly contained in the Tem subset, AE-specific CD8+ T cells encompassed naive, as well as T central memory, Tem and Temra cells.CONCLUSION: All together, these findings indicate a link between AE-specific CD8+ T cells and advanced liver fibrosis in patients with chronic HBV infection, and suggest that virus-specific and AE-specific CD8+ T cells exhibit distinct differentiation states and contribute in distinct ways to immunopathology
ANGPTL3 deficiency associates with the expansion of regulatory T cells with reduced lipid content
No full textAngiopoietin-like 3 (ANGPTL3) regulates lipid and glucose metabolism. Loss-of-function mutations in its gene, leading to ANGPTL3 deficiency, cause in humans the familial combined hypolipidemia type 2 (FHBL2) phenotype, characterized by very low concentrations of circulating lipoproteins and reduced risk of atherosclerotic cardiovascular disease. Whether this condition is accompanied by immune dysfunctions is unknown. Regulatory T cells (Tregs) are CD4 T lymphocytes endowed with immune suppressive and atheroprotective functions and sensitive to metabolic signals. By investigating FHBL2, we explored the hypothesis that Tregs expand in response to extreme hypolipidemia, through a modulation of the Treg-intrinsic lipid metabolism
The role of lipid metabolism in shaping the expansion and the function of regulatory T cells
No full textMetabolic inflammation, defined as a chronic low-grade inflammation, is implicated in numerous metabolic diseases. In recent years, the role of regulatory T cells (Tregs) as key controllers of metabolic inflammation has emerged, but our comprehension on how different metabolic pathways influence Treg functions needs a deeper understanding. Here we focus on how circulating and intracellular lipid metabolism, in particular cholesterol metabolism, regulates Treg homeostasis, expansion, and functions. Cholesterol is carried through the bloodstream by circulating lipoproteins (chylomicrons, very low-density lipoproteins, low-density lipoproteins). Tregs are equipped with a wide array of metabolic sensors able to perceive and respond to changes in the lipid environment through the activation of different intracellular pathways thus conferring to these cells a crucial metabolic and functional plasticity. Nevertheless, altered cholesterol transport, as observed in genetic dyslipidemias and atherosclerosis, impairs Treg proliferation and function through defective cellular metabolism. The intracellular pathway devoted to the cholesterol synthesis is the mevalonate pathway and several studies have shown that this pathway is essential for Treg stability and suppressive activity. High cholesterol concentrations in the extracellular environment may induce massive accumulation of cholesterol inside the cell thus impairing nutrients sensors and inhibiting the mevalonate pathway. This review summarizes the current knowledge regarding the role of circulating and cellular cholesterol metabolism in the regulation of Treg metabolism and functions. In particular, we will discuss how different pathological conditions affecting cholesterol transport may affect cellular metabolism in Tregs
Assessment of lipid load in tumor-infiltrating tregs by flow cytometry
No full textRegulatory T cells (Tregs), expressing the transcription factor Foxp3, are defined as immunosuppressive cells able to modulate a variety of immune cells in order to avoid unwanted and excessive immune responses; however, in the tumor context, Treg function contribute to inhibit immune surveillance, thus promoting cancer progression. In tumor microenvironment, where the availability of metabolic resources is strongly limited, Tregs are expanded and may exploit different metabolic routes to achieve a metabolic advantage, prevailing over effector cells. In this context an important role of lipid metabolism has been described thanks to the possibility to evaluate the intracellular lipid content selectively in tumor-infiltrating Tregs (TUM-Tregs). Taking into account the heterogeneous and complex build of tumor mass, we set-up a combined protocol that optimizes tumor-infiltrating lymphocytes (TIL) extraction from the tissue through a Percoll density gradient, and assesses ex vivo the lipid load in whole TUM-Treg population, evaluating by flow cytometry the incorporation of an intensely fluorescent lipophilic fluorophore able to specifically stain neutral lipids. This method provides an important advantage compared to the traditional technique based on microscopy, whose lipid level evaluation is limited to a tissue section, and hence may not be representative of the entire population
In adult X-CGD patients, regulatory T cells are expanded while activated T cells display a NOX2-independent ROS increase
No full text: The X-linked chronic granulomatous disease (X-CGD), a rare genetic disease characterised by recurrent infections, is caused by mutations of NOX2. Significant proportions of X-CGD patients display signs of immune dysregulation. Regulatory T cells (Tregs) are CD4+ T lymphocytes that expand in active inflammation and prevent autoimmune disorders. Here we asked whether X-CGD is associated to Treg dysfunctions in adult patients. To this aim, the frequency of Tregs was analysed through intracellular flow cytometry in a cohort of adult X-CGD patients, carriers and controls. We found that Tregs were significantly expanded and activated in blood of adult X-CGD patients, and this was associated with activation of conventional CD4+ T cells (Tconvs). T cell activation was characterised by accumulation of intracellular ROS, not derived from NOX2 but likely produced by cellular metabolism. The higher TNF production by Tconvs in X-CGD patients might contribute to the expansion of Tregs through the TNFR2 receptor. In summary, our data indicate that Tregs expand in adult X-CGD in response to immune activation, and that the increase of NOX2-independent ROS content is a feature of activated T cells
TNF Production or TNFR2 Expression Characterize Distinct States of Regulatory T Cells that Cooperate in Treg Expansion in Cancer and Chronic Inflammation
No full textTNF is a pleiotropic cytokine with immunomodulatory functions mediated by its interaction with the receptor TNFR2, highly expressed by Tregs. However, Tregs can also produce TNF, and an autocrine TNF-TNFR2 loop has been proposed. Here, we describe that both human and mouse Tregs produce TNF in physiological conditions, in several mouse organs, and in mouse models of chronic inflammation and cancer. However, TNF production and TNFR2 expression are differentially distributed: indeed, TNFR2+ and TNFR2− Treg subsets are, respectively, poor and strong TNF producers. The two subsets of TNFR2+ and TNFR2− Tregs partially maintain their different ability to produce TNF when separately stimulated ex vivo. However, when cocultured, the TNFR2+ cells greatly outnumber the TNFR2− counterpart and induce in TNFR2− cells the upregulation of Foxp3 and TNFR2, in association with the transfer of cytoplasmic material. Functionally, TNFR2+ Tregs display superior suppressive activity and survival in vitro, both related to an improved resistance to oxidative stress. Overall, our data indicate that Tregs exist in two states, respectively committed to TNF production or TNF sensing through TNFR2, which cooperate in promoting the suppressive function of the whole Treg pool
Distinct Blood and Visceral Adipose Tissue Regulatory T Cell and Innate Lymphocyte Profiles Characterize Obesity and Colorectal Cancer
No full textVisceral adipose tissue (VAT) is a main site where metabolic and immunologic processes interplay to regulate, at local and systemic level, the inflammatory status and immune response. Obesity-associated inflammation and immune dysfunctions are inextricably linked to tumor but, in spite of intense efforts, the mechanisms underpinning this association remain elusive. In this report, we characterized the profile of VAT-associated and circulating innate lymphocyte and regulatory T (Treg) cell subsets underlying inflammatory conditions, such as obesity and colorectal cancer (CRC). Analysis of NK, NKT-like, γδ T, and Treg cell populations in VAT and blood of healthy lean subjects revealed that CD56hi NK and OX40+ Treg cells are more abundant in VAT with respect to blood. Conversely, CD56dim NK and total Treg cells are most present in the circulation, while γδ T lymphocytes are uniformly distributed in the two compartments. Interestingly, a reduced frequency of circulating activated Treg cells, and a concomitant preferential enrichment of OX40-expressing Treg cells in VAT, were selectively observed in obese (Ob) subjects, and directly correlated with body mass index. Likewise, CRC patients were characterized by a specific enrichment of VAT-associated NKT-like cells. In addition, Ob and CRC-affected individuals shared a significant reduction of the Vγ9Vδ2/γδ T cell ratio at systemic level. The alterations in the relative proportions of Treg and NKT-like cells in VAT were found to correlate with the content of pro- and anti-inflammatory polyunsaturated fatty acids (PUFA), respectively. Overall, these results provide evidence for distinct alterations of the immune cell repertoire in the periphery with respect to the VAT microenvironment that uniquely characterize or are shared by different inflammatory conditions, such as obesity and CRC, and suggest that VAT PUFA composition may represent one of the factors that contribute to shape the immune phenotypes
Wi-Fi channel frequency response database for contactless human activity recognition
No full textThis database collects the channel frequency response (CFR) vectors captured through the Nexmon CSI extraction tool from an Asus RT-AC86U IEEE 802.11ac Wi-Fi router working with a total bandwidth of 80 MHz. The dataset is collected in three different environments, i.e., a bedroom, a living room and a University laboratory, while one person performs one among seven activities of interest within the room. The CFR data for the empty room (E) is also provided.
We obtained data from three volunteers (a male, and two females) while they were walking (W) or running (R) around, jumping (J) in place, sitting (L) or standing (S) somewhere in the room, sitting down and standing up (C) continuously, and doing arm gym (H).
Each CFR sample results in complex-valued channel information from 242 data sub-channels for each transmit-receive antennas pair. In our experiments, with one transmitter antenna and four at the monitoring device, each sample corresponds to four vectors of 242 complex values. Although the total number of sub-channels at 80 MHz is 256, each antenna vector has 242 components as the CFR is only provided for data sub-channels, namely sub-channels whose indexes are {-122, ..., -2} and {2, ..., 122}, i.e., no CFR value is provided for the control sub-channels. For more information about the setup, please, refer to the related publication.
This dataset was used to design and assess the performance of SHARP presented in the article ''SHARP: Environment and Person Independent Activity Recognition with Commodity IEEE 802.11 Access Points'' by Francesca Meneghello, Domenico Garlisi, Nicolò Dal Fabbro, Ilenia Tinnirello, Michele Rossi.
The Python source code is available at https://github.com/signetlabdei/SHARP.
If you use this dataset, please cite our paper: @misc{meneghello2022SHARP,
url = {https://arxiv.org/abs/2103.09924},
author = {Meneghello, Francesca and Garlisi, Domenico and Fabbro, Nicolò Dal and Tinnirello, Ilenia and Rossi, Michele},
title = {Environment and Person Independent Activity Recognition with a Commodity IEEE 802.11ac Access Point},
publisher = {arXiv},
year = {2021}
Evaluation of autophagy in lymphocyte populations during atherosclerotic plaque progression with flow cytometry
No full textAtherosclerosis is a chronic inflammatory disorder of the large arteries and represents the primary cause of heart disease and stroke. The exact cause of atherosclerosis is not known. A variety of studies show that autophagy deficiency may be pro-atherogenic and the role of autophagy in smooth muscle cells, macrophages and endothelial cells has been investigated. However, to date no studies addressed the effect of autophagy on lymphocyte subsets playing a role in plaque formation and development. The present project aims to better clarify the role played by autophagy in lymphocytes homeostasis in human atherosclerotic plaques. We characterized lymphocyte populations in different types of lesion by using flow cytometry. In particular, we detected OX40 as marker for conventional T cells promoting division and survival of effector and memory populations and pS6, a marker for an active mTOR pathway and autophagy detection. The understanding of the role of autophagy as a further mechanism underlying lymphocytes stability may open new therapeutic avenues for atherosclerosis
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