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https://www.readbyqxmd.com/read/29689377/ambient-particulate-matter-activates-the-aryl-hydrocarbon-receptor-in-dendritic-cells-and-enhances-th17-polarization
#1
Alejandro R Castañeda, Kent E Pinkerton, Keith J Bein, Alfonso Magaña-Méndez, Houa T Yang, Paul Ashwood, Christoph F A Vogel
The objective of this study was to explore the role of the aryl hydrocarbon receptor (AhR) in ambient particulate matter (PM)-mediated activation of dendritic cells (DCs) and Th17-immune responses in vitro. To assess the potential role of the AhR in PM-mediated activation of DCs, co-stimulation, and cytokine expression, bone marrow (BM)-derived macrophages and DCs from C57BL6 wildtype or AhR knockout (AhR-/- ) mice were treated with PM. Th17 differentiation was assessed via co-cultures of wildtype or AhR-/- BMDCs with autologous naive T cells...
April 21, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29689086/phase-i-ii-evaluation-of-rv1001-a-novel-pi3k%C3%AE-inhibitor-in-spontaneous-canine-lymphoma
#2
Heather L Gardner, Sarah B Rippy, Misty D Bear, Kim L Cronin, Heather Heeb, Holly Burr, Claire M Cannon, Kumar V Penmetsa, Srikant Viswanadha, Swaroop Vakkalanka, Cheryl A London
BACKGROUND: RV1001 is a novel, potent, and selective PI3Kδ inhibitor. The purpose of this study was to evaluate the safety and efficacy of RV1001 in canine Non-Hodgkin lymphoma (NHL). METHODS AND RESULTS: Inhibition of endogenous pAKT by RV1001 in primary canine NHL cells was determined by Western blotting. A phase I study of RV1001 was performed in 21 dogs with naïve and drug resistant T and B-cell NHL to assess safety, pharmacokinetic profile, and response to therapy...
2018: PloS One
https://www.readbyqxmd.com/read/29688840/active-and-persistent-cytomegalovirus-infections-affect-t-cells-in-young-adult-hiv-patients-commencing-antiretroviral-therapy
#3
Ibnu A Ariyanto, Riwanti Estiasari, Shelley Waters, Endah A T Wulandari, Sonia Fernandez, Silvia Lee, Patricia Price
Altered T cell profiles have been linked with metrics of persistent cytomegalovirus (CMV) infections in healthy aging and older HIV patients stable on antiretroviral therapy (ART). In this study, we use CMV DNA to identify active infections, and levels of CMV-reactive antibody to assess the persistent burden of CMV in a longitudinal study of 78 young adult patients beginning ART in Jakarta, Indonesia, with <200 CD4 T cells/μL. CMV antibodies, inflammatory markers (C-reactive protein [CRP], soluble interferon-α/β receptor) and T cell phenotypes were assessed before ART (V0) and after 1, 3, 6, and 12 months (V1-V12)...
April 24, 2018: Viral Immunology
https://www.readbyqxmd.com/read/29688585/reappraisal-of-classification-of-distal-cholangiocarcinoma-based-on-tumour-depth
#4
H Aoyama, T Ebata, M Hattori, M Takano, H Yamamoto, M Inoue, Y Asaba, M Ando, M Nagino
BACKGROUND: In the eighth edition of the AJCC cancer staging classification, the T system for distal cholangiocarcinoma (DCC) has been revised from a layer-based to a depth-based approach. The aim of this study was to propose an optimal T classification using a measured depth in resectable DCC. METHODS: Patients who underwent pancreatoduodenectomy for DCC at 32 hospitals between 2001 and 2010 were included. The distance between the level of the naive bile duct and the deepest cancer cells was measured as depth of invasion (DOI)...
April 24, 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29688533/plasma-cystatin-c-as-a-marker-for-estimated-glomerular-filtration-rate-assessment-in-hiv-1-infected-patients-treated-with-dolutegravir-based-art
#5
Romain Palich, Roland Tubiana, Besma Abdi, Fouzi Mestari, Marguerite Guiguet, Françoise Imbert-Bismut, Christine Katlama, Dominique Bonnefont-Rousselot, Corinne Isnard-Bagnis
Objectives: Inhibition of the organic cation transporter-2 renal tubule transporter by dolutegravir leads to serum creatinine increase. Serum cystatin C is a non-organic cation transporter-2-dependent marker, possibly enabling glomerular filtration rate (GFR) estimation under dolutegravir. Our goal was to evaluate the changes in creatinine- and cystatin C-based estimated GFR values before and after dolutegravir initiation. Methods: Creatinine and cystatin measurements were carried out on frozen plasma samples from HIV-1-infected patients, before and after dolutegravir initiation, between October 2016 and March 2017 at Pitié-Salpêtrière Hospital...
April 24, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29686686/autoimmune-lymphoproliferative-syndrome-fas-patients-have-an-abnormal-regulatory-t-cell-treg-phenotype-but-display-normal-natural-treg-suppressive-function-on-t-cell-proliferation
#6
Fabienne Mazerolles, Marie-Claude Stolzenberg, Olivier Pelle, Capucine Picard, Benedicte Neven, Alain Fischer, Aude Magerus-Chatinet, Frederic Rieux-Laucat
Objective: Autoimmune lymphoproliferative syndrome (ALPS) with FAS mutation (ALPS-FAS) is a nonmalignant, noninfectious, lymphoproliferative disease with autoimmunity. Given the central role of natural regulatory T cells (nTregs) in the control of lymphoproliferation and autoimmunity, we assessed nTreg-suppressive function in 16 patients with ALPS-FAS. Results: The proportion of CD25high CD127low Tregs was lower in ALPS-FAS patients than in healthy controls. This subset was correlated with a reduced CD25 expression in CD3+ CD4+ T cells from ALPS patients and thus an abnormally low proportion of CD25high FOXP3+ Helios+ T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29686677/mir-466a-targeting-of-tgf-%C3%AE-2-contributes-to-foxp3-regulatory-t-cell-differentiation-in-a-murine-model-of-allogeneic-transplantation
#7
William Becker, Mitzi Nagarkatti, Prakash S Nagarkatti
The promise of inducing immunological tolerance through regulatory T cell (Treg) control of effector T cell function is crucial for developing future therapeutic strategies to treat allograft rejection as well as inflammatory autoimmune diseases. In the current study, we used murine allograft rejection as a model to identify microRNA (miRNA) regulation of Treg differentiation from naïve CD4 cells. We performed miRNA expression array in CD4+ T cells in the draining lymph node (dLN) of mice which received syngeneic or allogeneic grafts to determine the molecular mechanisms that hinder the expansion of Tregs...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29686426/transcript-indexed-atac-seq-for-precision-immune-profiling
#8
Ansuman T Satpathy, Naresha Saligrama, Jason D Buenrostro, Yuning Wei, Beijing Wu, Adam J Rubin, Jeffrey M Granja, Caleb A Lareau, Rui Li, Yanyan Qi, Kevin R Parker, Maxwell R Mumbach, William S Serratelli, David G Gennert, Alicia N Schep, M Ryan Corces, Michael S Khodadoust, Youn H Kim, Paul A Khavari, William J Greenleaf, Mark M Davis, Howard Y Chang
T cells create vast amounts of diversity in the genes that encode their T cell receptors (TCRs), which enables individual clones to recognize specific peptide-major histocompatibility complex (MHC) ligands. Here we combined sequencing of the TCR-encoding genes with assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis at the single-cell level to provide information on the TCR specificity and epigenomic state of individual T cells. By using this approach, termed transcript-indexed ATAC-seq (T-ATAC-seq), we identified epigenomic signatures in immortalized leukemic T cells, primary human T cells from healthy volunteers and primary leukemic T cells from patient samples...
April 23, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29685903/posttranscriptional-regulation-of-t-helper-cell-fate-decisions
#9
REVIEW
Kai P Hoefig, Vigo Heissmeyer
T helper cell subsets orchestrate context- and pathogen-specific responses of the immune system. They mostly do so by secreting specific cytokines that attract or induce activation and differentiation of other immune or nonimmune cells. The differentiation of T helper 1 (Th1), Th2, T follicular helper, Th17, and induced regulatory T cell subsets from naive T cells depends on the activation of intracellular signal transduction cascades. These cascades originate from T cell receptor and costimulatory receptor engagement and also receive critical input from cytokine receptors that sample the cytokine milieu within secondary lymphoid organs...
April 23, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29684436/foxo-transcription-factors-in-t-cell-biology-and-tumor-immunity
#10
REVIEW
Chong T Luo, Ming O Li
The evolutionally conserved forkhead box O (Foxo) family of transcription factors is pivotal in the control of nutrient sensing and stress responses. Recent studies have revealed that the Foxo proteins have been rewired to regulate highly specialized T cell activities. Here, we review the latest advances in the understanding of how Foxo transcription factors control T cell biology, including T cell trafficking, naive T cell homeostasis, effector and memory responses, as well as the differentiation and function of regulatory T cells...
April 20, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29683841/monotypic-low-level-hiv-viremias-during-art-are-associated-with-disproportionate-production-of-x4-virions-and-systemic-immune-activation
#11
Marta E Bull, Caroline Mitchell, Jaime Soria, Sheila Styrchak, Corey Williams-Wietzikoski, Jillian Legard, Jennifer Mckernan-Mullin, Kelli Kraft, Frankline Onchiri, Joshua Stern, Sarah Holte, Kevin J Ryan, Edward P Acosta, Alberto La Rosa, Robert W Coombs, Eduardo Ticona, Lisa M Frenkel
OBJECTIVE: During effective antiretroviral therapy (ART), low-level plasma viremias (LLV) (HIV RNA >30-1000 copies/ml) can be detected intermittently. We hypothesized that systemic inflammation is associated with LLV either as the cause or result of the production of virions from clonally expanded cells. METHODS: Prospective cohort study of HIV-infected ART-naïve Peruvians enrolled prior to ART and followed for 2 years. Plasma HIV RNA and peripheral blood mononuclear cell (PBMC) HIV DNA concentrations were quantified pre-ART from individuals whose plasma HIV RNA was ART-suppressed...
April 19, 2018: AIDS
https://www.readbyqxmd.com/read/29682803/mechanobiological-mimicry-of-helper-t-lymphocytes-to-evaluate-cell-biomaterials-crosstalk
#12
Mohammad Mahdi Hasani-Sadrabadi, Fatemeh S Majedi, Steven J Bensinger, Benjamin M Wu, Louis-S Bouchard, Paul S Weiss, Alireza Moshaverinia
The unique properties of immune cells have inspired many efforts in engineering advanced biomaterials capable of mimicking their behaviors. However, an inclusive model capable of mimicking immune cells in different situations remains lacking. Such models can provide invaluable data for understanding immune-biomaterial crosstalk. Inspired by CD4+ T cells, polymeric microparticles with physicochemical properties similar to naïve and active T cells are engineered. A lipid coating is applied to enhance their resemblance and provide a platform for conjugation of desired antibodies...
April 23, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29682722/the-role-of-tgf-%C3%AE-in-th17-differentiation
#13
REVIEW
Song Zhang
Th17 cells play critical roles in inflammatory and autoimmune diseases. The lineage-specific transcription factor RORγt is the key regulator for Th17 cell fate commitment. A substantial number of studies have established the importance of TGF-β-dependent pathways in inducing RORγt expression and Th17 differentiation. TGF-β superfamily members TGF-β1, TGF-β3, or activin A, in concert with IL-6 or IL-21 differentiate naïve T cells into Th17 cells. Alternatively, Th17 differentiation can occur through TGF-β-independent pathways...
April 23, 2018: Immunology
https://www.readbyqxmd.com/read/29680462/recasting-human-v%C3%AE-1-lymphocytes-in-an-adaptive-role
#14
REVIEW
Martin S Davey, Carrie R Willcox, Alfie T Baker, Stuart Hunter, Benjamin E Willcox
γδ T cells are unconventional lymphocytes commonly described as 'innate-like' in function, which can respond in both a T cell receptor (TCR)-independent and also major histocompatibility complex (MHC)-unrestricted TCR-dependent manner. While the relative importance of TCR recognition had remained unclear, recent studies revealed that human Vδ1 T cells display unexpected parallels with adaptive αβ T cells. Vδ1 T cells undergo profound and highly focussed clonal expansion from an initially diverse and private TCR repertoire, most likely in response to specific immune challenges...
April 18, 2018: Trends in Immunology
https://www.readbyqxmd.com/read/29678809/delayed-immune-reconstitution-after-allogeneic-transplantation-increases-the-risks-of-mortality-and-chronic-gvhd
#15
Nelli Bejanyan, Claudio G Brunstein, Qing Cao, Aleksandr Lazaryan, Xianghua Luo, Julie Curtsinger, Rohtesh S Mehta, Erica Warlick, Sarah A Cooley, Bruce R Blazar, Jeffrey S Miller, Daniel Weisdorf, John E Wagner, Michael R Verneris
Slow immune reconstitution is a major obstacle to the successful use of allogeneic hematopoietic cell transplantation (allo-HCT). As matched sibling donor (MSD) allo-HCT is regarded as the gold standard, we evaluated the pace of immune reconstitution in 157 adult recipients of reduced-intensity conditioning followed by MSD peripheral blood HCT (n = 68) and compared these to recipients of umbilical cord blood (UCB; n = 89). At day 28, UCB recipients had fewer natural killer (NK) cells than MSD recipients, but thereafter, NK cell numbers (and their subsets) were higher in UCB recipients...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29677474/unraveling-the-complex-interplay-between-t-cell-metabolism-and-function
#16
Ramon I Klein Geltink, Ryan L Kyle, Erika L Pearce
Metabolism drives function, on both an organismal and a cellular level. In T cell biology, metabolic remodeling is intrinsically linked to cellular development, activation, function, differentiation, and survival. After naive T cells are activated, increased demands for metabolic currency in the form of ATP, as well as biomass for cell growth, proliferation, and the production of effector molecules, are met by rewiring cellular metabolism. Consequently, pharmacological strategies are being developed to perturb or enhance selective metabolic processes that are skewed in immune-related pathologies...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29672576/malnutrition-and-lipid-abnormalities-in-antiretroviral-na%C3%A3-ve-hiv-infected-adults-in-addis-ababa-a-cross-sectional-study
#17
Melaku Adal, Rawleigh Howe, Desta Kassa, Abraham Aseffa, Beyene Petros
BACKGROUND: Both under- and over-nutrition may occur among human immunodeficiency virus (HIV)-infected individuals and impact on the course of the acquired immune deficiency syndrome (AIDS) and its management due to the close interaction between immunity and nutrition. We investigated occurrence of undernutrition, excess weight and lipid abnormalities among antiretroviral naïve HIV-infected adults in Addis Ababa, Ethiopia. METHODS: A cross-sectional study on 594 antiretroviral therapy (ART) naïve HIV-infected adults was conducted in four hospitals in Addis Ababa from February to September 2013...
2018: PloS One
https://www.readbyqxmd.com/read/29672174/th9-cells-probable-players-in-ulcerative-colitis-pathogenesis
#18
Mojtaba Shohan, Shokrollah Elahi, Hedayatollah Shirzad, Mahmoud Rafieian-Kopaei, Nader Bagheri, Emad Soltani
T lymphocytes represent an important part of adaptive immune system undertaking different functions to regulate immune responses. CD4+ T cells are the most important activator cells in inflammatory conditions. Depending on the type of induced cells and inflamed sites, expression and activity of different subtypes of helper T cells are changed. Recent studies have confirmed the existence of a new subset of helper T lymphocytes called Th9. Naive T cells can differentiate into Th9 subtypes if they are exposed simultaneously by interleukin (IL) 4 and transforming growth factor β and also secondary activation of a complicated network of transcription factors such as interferon regulatory factor 4 (IRF4) and Smads which are essential for adequate induction of this phenotype...
April 19, 2018: International Reviews of Immunology
https://www.readbyqxmd.com/read/29670745/induction-of-immunity-following-vaccination-with-a-chemically-attenuated-malaria-vaccine-correlates-with-persistent-antigenic-stimulation
#19
Jennifer M Reiman, Sanjai Kumar, Ingrid B Rodriguez, Sedami Gnidehou, Koichi Ito, Danielle I Stanisic, Moses Lee, Virginia McPhun, Victoria Majam, Nicole M Willemsen, Michael R Batzloff, Amber I Raja, Brad Dooley, Stephen L Hoffman, Stephanie K Yanow, Michael F Good
Objectives: Blood stage malaria parasites attenuated with seco-cyclopropyl pyrrolo indole (CPI) analogues induce robust immunity in mice to homologous and heterologous malaria parasites and are being considered for the development of a human vaccine. However, it is not understood how attenuated parasites induce immunity. We showed that following vaccination, parasite DNA persisted in blood for several months, raising the possibility that ongoing immune stimulation may be critical. However, parasites were not seen microscopically beyond 24 h postvaccination...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29670615/distinct-in-vitro-t-helper-17-differentiation-capacity-of-peripheral-naive-t-cells-in-rheumatoid-and-psoriatic-arthritis
#20
Eszter Baricza, Nikolett Marton, Panna Királyhidi, Orsolya Tünde Kovács, Ilona Kovácsné Székely, Eszter Lajkó, Lászó Kőhidai, Bernadett Rojkovich, Barbara Érsek, Edit Irén Buzás, György Nagy
Background: The T-helper 17 (Th17) cells have a prominent role in inflammation as well as in bone and join destruction in both rheumatoid and psoriatic arthritis (RA and PsA). Here, we studied Th17 cell differentiation in RA and PsA. Methods: Blood samples from healthy donors, RA and PsA patients were collected. CD45RO- (naive) and CD45RO+ (memory) T cells were isolated from peripherial blood mononuclear cell by magnetic separation. Naive T cells were stimulated with anti-CD3, anti-CD28, and goat anti-mouse IgG antibodies and treated with transforming grow factor beta, interleukin (IL)-6, IL-1β , and IL-23 cytokines and also with anti-IL-4 antibody...
2018: Frontiers in Immunology
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