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T cell inhibitory pathway

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https://www.readbyqxmd.com/read/28644433/ctla-4-mediated-posttranslational-modifications-direct-cytotoxic-t-lymphocyte-differentiation
#1
Holger Lingel, Josef Wissing, Aditya Arra, Denny Schanze, Stefan Lienenklaus, Frank Klawonn, Mandy Pierau, Martin Zenker, Lothar Jänsch, Monika C Brunner-Weinzierl
The blockade of inhibitory receptors such as CTLA-4 (CD152) is being used as immune-checkpoint therapy, offering a powerful strategy to restore effective immune responses against tumors. To determine signal components that are induced under the control of CTLA-4 we analyzed activated murine CD8(+) T cells by quantitative proteomics. Accurate mass spectrometry revealed that CTLA-4 engagement led to central changes in the phosphorylation of proteins involved in T-cell differentiation. Beside other targets, we discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 (PDCD4) as a result of FoxO1 nuclear re-localization...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28642997/pd-1-and-cancer-molecular-mechanisms-and-polymorphisms
#2
REVIEW
Arash Salmaninejad, Vahid Khoramshahi, Alireza Azani, Ehsan Soltaninejad, Saeed Aslani, Mohammad Reza Zamani, Masoud Zal, Abolfazl Nesaei, Sayed Mostafa Hosseini
The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers...
June 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28639625/microrna-34a-dependent-regulation-of-axl-controls-the-activation-of-dendritic-cells-in-inflammatory-arthritis
#3
Mariola Kurowska-Stolarska, Stefano Alivernini, Emma Garcia Melchor, Aziza Elmesmari, Barbara Tolusso, Clare Tange, Luca Petricca, Derek S Gilchrist, Gabriele Di Sante, Chantal Keijzer, Lynn Stewart, Clara Di Mario, Vicky Morrison, James M Brewer, Duncan Porter, Simon Milling, Ronald D Baxter, David McCarey, Elisa Gremese, Greg Lemke, Gianfranco Ferraccioli, Charles McSharry, Iain B McInnes
Current treatments for rheumatoid arthritis (RA) do not reverse underlying aberrant immune function. A genetic predisposition to RA, such as HLA-DR4 positivity, indicates that dendritic cells (DC) are of crucial importance to pathogenesis by activating auto-reactive lymphocytes. Here we show that microRNA-34a provides homoeostatic control of CD1c(+) DC activation via regulation of tyrosine kinase receptor AXL, an important inhibitory DC auto-regulator. This pathway is aberrant in CD1c(+) DCs from patients with RA, with upregulation of miR-34a and lower levels of AXL compared to DC from healthy donors...
June 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28638725/administration-of-a-vasoactive-intestinal-peptide-antagonist-enhances-the-autologous-anti-leukemia-t-cell-response-in-murine-models-of-acute-leukemia
#4
Christopher T Petersen, Jian-Ming Li, Edmund K Waller
Vasoactive intestinal peptide (VIP) is a neuroendocrine peptide hormone that has potent anti-inflammatory activities. VIP signaling through its receptor VPAC1 on T cells leads to reduced proliferation and a reduction in pro-inflammatory cytokine secretion. We report here that inhibition of the VIP pathway with a peptide antagonist significantly enhances a T-cell-dependent, autologous anti-leukemia response in murine models of acute myeloid leukemia and T lymphoblastic leukemia. Subcutaneous administration of the VIP antagonist, VIPhyb, resulted in reduced tumor burden and significantly enhanced survival (30-50% survival) over vehicle-treated controls (0-20% survival)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28633979/zerumbone-modulates-cd1d-expression-and-lipid-antigen-presentation-pathway-in-breast-cancer-cells
#5
Ritis K Shyanti, Anuradha Sehrawat, Shivendra V Singh, J P N Mishra, Rana P Singh
Natural Killer T (NKT) cells based cancer immunotherapy is an evolving area of cancer therapy, but tumors escape from this treatment modality by altering CD1d expression and its antigen presentation pathway. Here, we have studied the relation of CD1d expression in various breast cancer cell lines to their viability and progression. We observed a novel phenomenon that CD1d expression level increases with the progressive stage of the cancer. A small molecule, zerumbone (ZER) caused down-regulation of CD1d that was accompanied by breast cancer cell growth in vitro...
June 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28633436/membrane-androgen-receptor-zip9-induces-croaker-ovarian-cell-apoptosis-via-stimulatory-g-protein-alpha-subunit-and-mapkinase-signaling
#6
Aubrey Converse, Chenan Zhang, Peter Thomas
Recent studies show that androgen-induced apoptosis in Atlantic croaker primary granulosa/theca (G/T) cells and in human breast and prostate cancer cell lines is mediated by the novel membrane androgen receptor ZIP9 which belongs to the SLC39A zinc transporter family. However, the apoptotic signaling pathways remain unclear because ZIP9 activates an inhibitory G protein in human cancer cells, whereas recombinant croaker ZIP9 activates a stimulatory G protein (Gs) in transfected cancer cells. Here we investigated androgen-dependent apoptotic pathways in order to identify the signaling pathways regulated through wild-type croaker ZIP9 in ovarian follicle cells...
June 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28629373/blimp-1-impairs-t-cell-function-via-upregulation-of-tigit-and-pd-1-in-patients-with-acute-myeloid-leukemia
#7
Liuluan Zhu, Yaxian Kong, Jianhong Zhang, David F Claxton, W Christopher Ehmann, Witold B Rybka, Neil D Palmisiano, Ming Wang, Bei Jia, Michael Bayerl, Todd D Schell, Raymond J Hohl, Hui Zeng, Hong Zheng
BACKGROUND: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28618355/chemical-constituents-from-the-fruits-of-ligustrum-japonicum-and-their-inhibitory-effects-on-t-cell-activation
#8
Quynh-Mai Thi Ngo, Hyun-Su Lee, Van Thu Nguyen, Jeong Ah Kim, Mi Hee Woo, Byung Sun Min
A previously undescribed nor-dammarane, 3β,20,23-trihydroxy-24,25,26,27-tetranordammarane; three previously undescribed secoiridoid glycosides, ligujaponosides A-B, and iso-oleonuzhenide; and twenty three known compounds, were isolated from the fruits of Ligustrum japonicum Thunb. Their chemical structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, and HRMS. The isolated compounds were screened for immunosuppressive effects on T activated cells by evaluating interleukin-2 (IL-2) production...
June 12, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28617942/withasteroid-b-from-d-metel-l-regulates-immune-responses-by-modulating-the-jak-stat-pathway-and-the-il-17-ror%C3%AE-t-il-10-foxp3-ratio
#9
Yang Su, Qiuhong Wang, Bingyou Yang, Lun Wu, Genhong Cheng, Haixue Kuang
Datura metel L. is a medicinal herb that contains withasteroids and has a wide range of biological activities. We isolated 7 withasteroids from the flowers of D. metel L(1) . and examined their ability to inhibit immune responses in vitro and in vivo. Among the withasteroids, B2(2) exhibited the strongest inhibitory effect on immune responses comparing B2 with other isolated compounds from D. metel L., including suppressing the differentiation of CD4(+3) T cells by inhibiting the expression and production of T cell lineage-specific master regulators and cytokines and directly suppressing the cytokine-induced JAK/STAT(4) signaling pathways...
June 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28614296/selective-depletion-of-uropathogenic-e-coli-from-the-gut-by-a-fimh-antagonist
#10
Caitlin N Spaulding, Roger D Klein, Ségolène Ruer, Andrew L Kau, Henry L Schreiber, Zachary T Cusumano, Karen W Dodson, Jerome S Pinkner, Daved H Fremont, James W Janetka, Han Remaut, Jeffrey I Gordon, Scott J Hultgren
Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) affect 150 million people annually. Despite effective antibiotic therapy, 30-50% of patients experience recurrent UTIs. In addition, the growing prevalence of UPEC that are resistant to last-line antibiotic treatments, and more recently to carbapenems and colistin, make UTI a prime example of the antibiotic-resistance crisis and emphasize the need for new approaches to treat and prevent bacterial infections. UPEC strains establish reservoirs in the gut from which they are shed in the faeces, and can colonize the periurethral area or vagina and subsequently ascend through the urethra to the urinary tract, where they cause UTIs...
June 14, 2017: Nature
https://www.readbyqxmd.com/read/28611673/reversing-egfr-mediated-immunoescape-by-targeted-monoclonal-antibody-therapy
#11
REVIEW
Fernando Concha-Benavente, Robert L Ferris
Uncontrolled growth is a signature of carcinogenesis, in part mediated by overexpression or overstimulation of growth factor receptors. The epidermal growth factor receptor (EGFR) mediates activation of multiple oncogenic signaling pathways and escape from recognition by the host immune system. We discuss how EGFR signaling downregulates tumor antigen presentation, upregulates suppressive checkpoint receptor ligand programmed death ligand (PD-L1), induces secretion of inhibitory molecules such as transforming growth factor beta (TGFβ) and reprograms the metabolic pathways in cancer cells to upregulate aerobic glycolysis and lactate secretion that ultimately lead to impaired cellular immunity mediated by natural killer (NK) cell and cytotoxic T lymphocytes (CTL)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28605877/ginsenoside-rb2-inhibits-osteoclast-differentiation-through-nuclear-factor-kappab-and-signal-transducer-and-activator-of-transcription-protein-3-signaling-pathway
#12
Fei Cong, Jian Liu, Chunmei Wang, Zhi Yuan, Long Bi, Jidong Liang, Ke Su, Yucheng Qiu, Tao Song, Jinzhu Fan, Gao Chao
Ginsenoside-Rb2 (Rb2) is a 20(S)-protopanaxadiol glycoside extracted from ginseng possessing various bioactivities which has drawn considerable interest regarding the area of bone metabolism. However, the effect of Rb2 on osteoclast differentiation remains unknown. In this study, we aimed to investigate the potential role of Rb2 in regulating osteoclast differentiation and the underlying molecular mechanisms. Osteoclast differentiation was induced by receptor activator nuclear factor-kappaB (NF-κB) ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in mouse RAW 264...
June 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28601050/inhibition-of-apoptosis-and-proliferation-in-t-cells-by-immunosuppressive-silymarine
#13
Ehsan Almasi, Marjan Gharagozloo, Nahid Eskandari, Afshin Almasi, Ali Mohammad Sabzghabaee
Silybum marianum, is known to have anti-inflammatory, hepatoprotective and anticarciogenic effects. The aim of this study was to compare effects of Silymarin, Rapamycin and FK506 on proliferation and apoptosis of human T cells stimulated with Con A. Peripheral blood mononuclear cells (PBMC) were stimulated with concavalin A (Con A) (5µg/mL) and then treated with different inhibitors (silymarin, rapamycin and FK506) in various concentrations (5 days). Cells were examined using carboxyfluorescein succinimidyl ester (CFSE) assay for proliferation...
April 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28596283/combined-targeting-of-stat3-and-stat5-a-novel-approach-to-overcome-drug-resistance-in-chronic-myeloid-leukemia
#14
Karoline V Gleixner, Mathias Schneeweiss, Gregor Eisenwort, Daniela Berger, Harald Herrmann, Katharina Blatt, Georg Greiner, Konstantin Byrgazov, Gregor Hoermann, Marina Konopleva, Islam Waliul, Abbarna A Cumaraswamy, Patrick T Gunning, Hiroshi Maeda, Richard Moriggl, Michael Deininger, Thomas Lion, Michael Andreeff, Peter Valent
In chronic myeloid leukemia, resistance against BCR-ABL1 tyrosine kinase inhibitors can develop because of BCR-ABL1 mutations, activation of additional pro-oncogenic pathways, and stem cell resistance. Drug combinations covering a broad range of targets may overcome resistance. CDDO-Me is a drug that inhibits the survival of leukemic cells by targeting different pro-survival molecules, including STAT3. We found that CDDO-Me inhibits proliferation and survival of tyrosine kinase inhibitor-resistant BCR-ABL1+ cell lines and primary leukemic cells, including cells harboring BCR-ABL1T315I or T315I+ compound mutations...
June 8, 2017: Haematologica
https://www.readbyqxmd.com/read/28589725/dual-targeting-nanoparticle-stimulates-the-immune-system-to-inhibit-tumor-growth
#15
Alyssa K Kosmides, John-William Sidhom, Andrew Fraser, Catherine A Bessell, Jonathan P Schneck
We describe the development of a nanoparticle platform that overcomes the immunosuppressive tumor microenvironment. These nanoparticles are coated with two different antibodies that simultaneously block the inhibitory checkpoint PD-L1 signal and stimulate T cells via the 4-1BB co-stimulatory pathway. These "immunoswitch" particles significantly delay tumor growth and extend survival in multiple in vivo models of murine melanoma and colon cancer in comparison to the use of soluble antibodies or nanoparticles separately conjugated with the inhibitory and stimulating antibodies...
June 7, 2017: ACS Nano
https://www.readbyqxmd.com/read/28588487/gyf-21-an-epoxide-2-2-phenethyl-chromone-derivative-suppresses-innate-and-adaptive-immunity-via-inhibiting-stat1-3-and-nf-%C3%AE%C2%BAb-signaling-pathways
#16
Ran Guo, Yun-Fang Zhao, Jun Li, Yu-Fan Gu, Hui-Xia Huo, Shan-Shan Li, Yue-Lin Song, Zhi-Xiang Zhu, Peng-Fei Tu
Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system characterized by demyelinating plaques and axonal loss. Inhibition on over activation of innate and adaptive immunity provides a rationale strategy for treatment of multiple sclerosis. In the present study, we investigated the inhibitory effects of GYF-21, an epoxide 2-(2-phenethyl)-chromone derivative isolated from Chinese agarwood, on innate and adaptive immunity for revealing its potential to treat multiple sclerosis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28585775/the-roles-of-the-pd-1-pd-l1-pathway-at-immunologically-privileged-sites
#17
Li-Ling Wang, Zhi-Hui Li, Xiao-Hui Hu, Kahinho P Muyayalo, Yong-Hong Zhang, Ai-Hua Liao
The PD-1/PD-L1 pathway plays a vital role in the maintenance of peripheral tolerance, promoting the development and function of regulatory T cells, and maintaining the quiescence of autoreactive T cells. Abnormalities in this inhibitory pathway are involved in the pathogenesis of some disorders such as tumours, autoimmune diseases, pregnancy complications, and transplantation rejection. Immune privilege represents a special immunological condition, where foreign antigens can be tolerated and do not elicit an immune response...
June 6, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28580587/heme-oxygenase-1-directly-binds-stat3-to-control-the-generation-of-pathogenic-th17-cells-during-neutrophilic-airway-inflammation
#18
Xiaoliang Lin, Jiajia Lv, Jie Lv, Caixia Di, Yanjie Zhang, Tong Zhou, Junling Liu, Zhenwei Xia
BACKGROUND: Specific JAK/STAT pathways play a critical role in the functional differentiation of distinct Th subsets. Previously, we showed that HO-1, a stress-inducible protein, inhibits Th17 cell differentiation and alleviates neutrophilic airway inflammation, but the responsible molecular basis remains unclear. METHODS: We employed Th17-skewing differentiation and NEA mouse models to study the role of HO-1 regulating IL-6-STAT3-RORγt/SOCS3 signaling pathway to control Th17 cell-mediated neutrophilic airway inflammation...
June 5, 2017: Allergy
https://www.readbyqxmd.com/read/28572863/epi-drugs-in-combination-with-immunotherapy-a-new-avenue-to-improve-anticancer-efficacy
#19
REVIEW
Roberta Mazzone, Clemens Zwergel, Antonello Mai, Sergio Valente
Immune checkpoint factors, such as programmed cell death protein-1/2 (PD-1, PD-2) or cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) receptors, are targets for monoclonal antibodies (MAbs) developed for cancer immunotherapy. Indeed, modulating immune inhibitory pathways has been considered an important breakthrough in cancer treatment. Although immune checkpoint blockade therapy used to treat malignant diseases has provided promising results, both solid and haematological malignancies develop mechanisms that enable themselves to evade the host immune system...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28572054/targeting-the-programmed-cell-death-1-pathway-in-rheumatoid-arthritis
#20
REVIEW
Sabina Sandigursky, Gregg J Silverman, Adam Mor
Since the introduction of TNF-α inhibitors and other biologic agents, the clinical outcome for many treated rheumatoid arthritis patients has significantly improved. However, there are still a substantial proportion of patients that are intolerant, or have inadequate responses, with current agents that have become the standards of care. While the majority of these agents are designed to affect the inflammatory features of the disease, there are also agents in the clinic that instead target lymphocyte subsets (e...
May 29, 2017: Autoimmunity Reviews
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