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https://www.readbyqxmd.com/read/29030484/aubergine-and-pirnas-promote-germline-stem-cell-self-renewal-by-repressing-the-proto-oncogene-cbl
#1
Patricia Rojas-Ríos, Aymeric Chartier, Stéphanie Pierson, Martine Simonelig
PIWI proteins play essential roles in germ cells and stem cell lineages. In Drosophila, Piwi is required in somatic niche cells and germline stem cells (GSCs) to support GSC self-renewal and differentiation. Whether and how other PIWI proteins are involved in GSC biology remains unknown. Here, we show that Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for their self-renewal and differentiation. Aub needs to be loaded with piRNAs to control GSC self-renewal and acts through direct mRNA regulation...
October 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29025909/histone-deacetylase-inhibitors-downregulate-ccr4-expression-and-decrease-mogamulizumab-efficacy-in-ccr4-positive-mature-t-cell-lymphomas
#2
Akihiro Kitadate, Sho Ikeda, Fumito Abe, Naoto Takahashi, Norio Shimizu, Kosei Matsue, Hiroyuki Tagawa
HDAC inhibitors are promising agents for various T-cell lymphomas, including cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and adult T-cell lymphoma/leukemia. CCR4 is an important therapeutic target molecule because mogamulizumab, an anti-CCR4 antibody, has shown promising efficacy against various T-cell lymphomas. In this study, we examined the in vitro synergistic effects of mogamulizumab and HDAC inhibitors against various T-cell lymphomas. First, we examined the expression of CCR4 mRNA and surface CCR4 in various T-cell lymphoma cell lines and found it was downregulated upon treatment with vorinostat, a pan-HDAC inhibitor...
October 12, 2017: Haematologica
https://www.readbyqxmd.com/read/29024811/cnot2-promotes-proliferation-and-angiogenesis-via-vegf-signaling-in-mda-mb-231-breast-cancer-cells
#3
Eun Jung Sohn, Deok-Beom Jung, HyoJung Lee, In Han, Jihyun Lee, Hyemin Lee, Sung-Hoon Kim
Here the underlying role of CNOT2, a subunit of CCR4-NOT complex, was elucidated in cancer progression. CNOT2 was overexpressed in HIT-T15, ASPC-1, BXPC-3, PC-3, LNCaP, MCF-7 and MDA-MB-231 cell lines, which was confirmed by Tissue array in various human tumor tissues. Also, CNOT2 depletion suppressed proliferation and colony formation of MDA-MB-231 cells. Of note, microarray revealed decreased expression of CNOT2, VEGF-A, HIF2 alpha (<0.5 fold) and increased expression of UMOD1, LOC727847, MMP4, hCG and other genes (>2...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29020986/colorectal-cancer-infiltrating-t-lymphocytes-display-a-distinct-chemokine-receptor-expression-profile
#4
Ann-Britt Löfroos, Mohammad Kadivar, Sabina Resic Lindehammer, Jan Marsal
BACKGROUND: T lymphocytes exert important homeostatic functions in the healthy intestinal mucosa, whereas in case of colorectal cancer (CRC), infiltration of T lymphocytes into the tumor is crucial for an effective anti-tumor immune response. In both situations, the recruitment mechanisms of T lymphocytes into the tissues are essential for the immunological functions deciding the outcome. The recruitment of T lymphocytes is largely dependent on their expression of various chemokine receptors...
October 11, 2017: European Journal of Medical Research
https://www.readbyqxmd.com/read/28978842/molecular-pathogenesis-and-its-therapeutic-implication-for-atl
#5
Kenji Ishitsuka
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1). HTLV-1 related proteins Tax and HTLV-1 bZIP factor induce immortalization and transformation of HTLV-1-infected T-lymphocytes and eventually induce clonal proliferation. One of the apparent molecular features in ATL cells is abundant genomic abnormalities targeting characteristic pathways, including T-cell receptor signaling and the NF-κB pathway, G-protein coupled-receptor, including CCR4, and transcriptional regulation...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978570/enhancer-profiling-identifies-critical-cancer-genes-and-characterizes-cell-identity-in-adult-t-cell-leukemia
#6
Regina Wan Ju Wong, Phuong Cao Thi Ngoc, Wei Zhong Leong, Alice Wei Yee Yam, Tinghu Zhang, Kaori Asamitsu, Shinsuke Iida, Takashi Okamoto, Ryuzo Ueda, Nathanael S Gray, Takashi Ishida, Takaomi Sanda
A number of studies have recently demonstrated that "super-enhancers", which are large cluster of enhancers typically marked by a high level of acetylation of histone H3 lysine 27 and mediator bindings, are frequently associated with genes that control and define cell identity during normal development. Super-enhancers are also often enriched at cancer genes in various malignancies. Identification of such enhancers would pinpoint critical factors that directly contribute to pathogenesis. Here, we performed enhancer profiling using primary leukemia samples from adult T-cell leukemia/lymphoma (ATL), which is a genetically heterogeneous intractable cancer...
October 4, 2017: Blood
https://www.readbyqxmd.com/read/28964722/a-t-cell-specific-deletion-of-hdac1-protects-against-experimental-autoimmune-encephalomyelitis
#7
Lisa Göschl, Teresa Preglej, Patricia Hamminger, Michael Bonelli, Liisa Andersen, Nicole Boucheron, Alexandra F Gülich, Lena Müller, Victoria Saferding, Ilgiz A Mufazalov, Kiyoshi Hirahara, Christian Seiser, Patrick Matthias, Thomas Penz, Michael Schuster, Christoph Bock, Ari Waisman, Günter Steiner, Wilfried Ellmeier
Multiple sclerosis (MS) is a human neurodegenerative disease characterized by the invasion of autoreactive T cells from the periphery into the CNS. Application of pan-histone deacetylase inhibitors (HDACi) ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model for MS, suggesting that HDACi might be a potential therapeutic strategy for MS. However, the function of individual HDAC members in the pathogenesis of EAE is not known. In this study we report that mice with a T cell-specific deletion of HDAC1 (using the Cd4-Cre deleter strain; HDAC1-cKO) were completely resistant to EAE despite the ability of HDAC1cKO CD4(+) T cells to differentiate into Th17 cells...
September 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28959024/up-regulation-of-chemokine-receptor-ccr4-is-associated-with-human-hepatocellular-carcinoma-malignant-behavior
#8
Xi Cheng, Huo Wu, Zhi-Jian Jin, Ding Ma, Stanley Yuen, Xiao-Qian Jing, Min-Min Shi, Bai-Yong Shen, Cheng-Hong Peng, Ren Zhao, Wei-Hua Qiu
Studies indicate that the chemokine receptor is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, we initially demonstrated that CCR4 is overexpressed in HCC specimens, and its elevation in HCC tissues positively correlates with tumor capsule breakthrough and vascular invasion. Although overexpression of CCR4 failed to influent proliferation of HCC cells in vitro apparently, the prominent acceleration on HCC tumor growth in vivo was remarkable. The underlying mechanism may be involved in neovascularization...
September 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28950145/determination-of-poor-prognostic-immune-features-of-tumour-microenvironment-in-non-smoking-patients-with-lung-adenocarcinoma
#9
Tomonari Kinoshita, Chie Kudo-Saito, Reiko Muramatsu, Tomonobu Fujita, Miyuki Saito, Haruna Nagumo, Toshiharu Sakurai, Shinobu Noji, Emi Takahata, Tomonori Yaguchi, Nobuo Tsukamoto, Yuichiro Hayashi, Kaoru Kaseda, Ikuo Kamiyama, Takashi Ohtsuka, Kenji Tomizawa, Masaki Shimoji, Tetsuya Mitsudomi, Hisao Asamura, Yutaka Kawakami
We have previously demonstrated that the prognostic significance of tumour-infiltrating CD8(+) T cells significantly differs according to histological type and patient smoking habits in non-small cell lung cancer (NSCLC). This work suggested that infiltrating CD8(+) T cells may not be activated sufficiently in the immunosuppressive microenvironment in non-smokers with adenocarcinoma. To understand the immunogenic microenvironment in NSCLC, we characterised immune cells comprehensively by performing an immunohistochemical evaluation using an alternative counting method and multicolour staining method (n = 234), and assessed immune-related gene expression by using genetic analytical approaches (n = 58)...
September 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28949051/distinct-peripheral-vs-mucosal-t-cell-phenotypes-in-chlamydia-infected-women
#10
Brian M O Ogendi, Rakesh K Bakshi, Steffanie Sabbaj, LaDraka' Brown, Jeannette Y Lee, Richa Kapil, William M Geisler
PROBLEM: Differences in circulating (peripheral) and mucosal T-cell phenotypes in chlamydia-infected women remain largely unknown. METHOD OF STUDY: Thirteen paired mononuclear cell specimens from blood and cervicovaginal lavages collected from chlamydia-infected women were stained and analyzed using ten-color cell surface flow cytometry for T-cell distribution, activation status, homing, and T helper (Th)-associated chemokine receptors (CKRs). RESULTS: A higher proportion of genital mucosal T-cells were activated (CD38(+) HLA-DR(+) ) and expressed CCR5 and Th1-associated CKR CXCR3(+) CCR5(+) compared to peripheral T-cells, but a lower proportion of mucosal T-cells expressed homing CKR CCR7, Th-2 associated CKR CCR4, and CXCR3(+) CCR4(+) for both T-cell subsets...
September 26, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28947948/discovery-of-azd-2098-and-azd-1678-two-potent-and-bioavailable-ccr4-receptor-antagonists
#11
Nicholas Kindon, Glen Andrews, Andrew Baxter, David Cheshire, Paul Hemsley, Timothy Johnson, Yu-Zhen Liu, Dermot McGinnity, Mark McHale, Antonio Mete, James Reuberson, Bryan Roberts, John Steele, Barry Teobald, John Unitt, Deborah Vaughan, Iain Walters, Michael J Stocks
N-(5-Bromo-3-methoxypyrazin-2-yl)-5-chlorothiophene-2-sulfonamide 1 was identified as a hit in a CCR4 receptor antagonist high-throughput screen (HTS) of a subset of the AstraZeneca compound bank. As a hit with a lead-like profile, it was an excellent starting point for a CCR4 receptor antagonist program and enabled the rapid progression through the Lead Identification and Lead Optimization phases resulting in the discovery of two bioavailable CCR4 receptor antagonist candidate drugs.
September 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28941492/replenishing-regulatory-t-cells-to-halt%C3%A2-depigmentation-in-vitiligo
#12
REVIEW
I Caroline Le Poole, Shikhar Mehrotra
Vitiligo is a cutaneous autoimmune disease, especially devastating to patients with darker skin tones because of the contrast between unaffected and lesional skin. We studied immune cells infiltrating vitiligo skin and found very few regulatory T cells (Tregs). Vitiligo was not associated with a reduced frequency or function of circulating Tregs. To manipulate Treg function, we used mouse models expressing melanocyte-reactive TCRs, following changes in pelage color. We also isolated splenocytes to measure Treg function and evaluated cutaneous Treg abundance...
October 2017: Journal of Investigative Dermatology. Symposium Proceedings
https://www.readbyqxmd.com/read/28940014/clinicopathological-analysis-in-ptcl-nos-with-cadm1-expression
#13
Takeharu Kato, Hiroaki Miyoshi, Seiichiro Kobayashi, Noriaki Yoshida, Yoshitaka Imaizumi, Masao Seto, Kaoru Uchimaru, Yasushi Miyazaki, Koichi Ohshima
Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), is a heterogeneous disease with respect to clinicopathological features. Cell adhesion molecule 1 (CADM1) has been reported to be ectopically expressed in adult T cell leukaemia/lymphoma (ATLL). However, the frequency of CADM1 expression remains unknown in peripheral T cell lymphomas. In the current study, CADM1 expression was analysed in 88 PTCL-NOS patients. CADM1 was expressed in 14 of 88 (15.9%) PTCL-NOS cases, and its expression was associated with C-C chemokine receptor type 4 (CCR4) expression and nuclear atypia...
September 22, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28929622/endonuclease-regnase-1-monocyte-chemotactic-protein-1-induced-protein-1-mcpip1-in-controlling-immune-responses-and-beyond
#14
REVIEW
Osamu Takeuchi
The activation of inflammatory cells is controlled at transcriptional and posttranscriptional levels. Posttranscriptional regulation modifies mRNA stability and translation, allowing for elaborate control of proteins required for inflammation, such as proinflammatory cytokines, prostaglandin synthases, cell surface co-stimulatory molecules, and even transcriptional modifiers. Such regulation is important for coordinating the initiation and resolution of inflammation, and is mediated by a set of RNA-binding proteins (RBPs), including Regnase-1, Roquin, Tristetraprolin (TTP), and AU-rich elements/poly(U)-binding/degradation factor 1 (AUF1)...
September 20, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28924126/development-of-epstein-barr-virus-related-primary-diffuse-large-b-cell-lymphoma-of-the-central-nervous-system-in-a-patient-with-peripheral-t-cell-lymphoma-not-otherwise-specified-after-mogamulizumab-treatment
#15
Hiroaki Tanaka, Hanako Aoki, Yasumasa Sugita, Ryo Shimizu, Katsunari Kiko, Hidetoshi Mochida, Yoshio Suzuki
Mogamulizumab is a defucosylated humanized anti-CC chemokine receptor type 4 (CCR4) antibody that exerts an anti-tumor immune effect against various tumors through a suppressive effect on regulatory T-cells. We herein report a patient with peripheral T-cell lymphoma who developed Epstein-Barr virus (EBV)-related primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) after mogamulizumab therapy. Our experience should alert physicians to the possibility of the development of EBV-related CNS DLBCL in patients treated for primary lymphoma and suggests that the anti-tumor immune effect of mogamulizumab is ineffective for the prophylaxis of EBV-related lymphomas...
September 15, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28918288/th9-cells-promote-antitumor-immunity-via-il-9-and-il-21-and-demonstrate-atypical-cytokine-expression-in-breast-cancer
#16
Fa-Ping You, Jian Zhang, Tao Cui, Rui Zhu, Chong-Qing Lv, Hai-Tao Tang, Di-Wen Sun
Breast cancer is a major cause of cancer-related death in women. Antitumor T cell responses play critical therapeutic roles, including direct cytotoxicity mediated by CD8(+) T cells and immunomodulatory roles mediated by CD4(+) T cells. The IL-9-expressing Th9 cells are recently found to present antitumor immunity in melanoma and lung adenocarcinoma. In this study, we found that IL-9 expression in the serum and in circulating CD4(+) T cells were significantly upregulated in breast cancer patients compared to healthy controls...
November 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28912492/epicutaneous-allergen-application-preferentially-boosts-specific-t-cell-responses-in-sensitized-patients
#17
Raffaela Campana, Katharina Moritz, Angela Neubauer, Hans Huber, Rainer Henning, Tess M Brodie, Alexandra Kaider, Federica Sallusto, Stefan Wöhrl, Rudolf Valenta
The effects of epicutaneous allergen administration on systemic immune responses in allergic and non-allergic individuals has not been investigated with defined allergen molecules. We studied the effects of epicutaneous administration of rBet v 1 and rBet v 1 fragments on systemic immune responses in allergic and non-allergic subjects. We conducted a clinical trial in which rBet v 1 and two hypoallergenic rBet v 1 fragments were applied epicutaneously by atopy patch testing (APT) to 15 birch pollen (bp) allergic patients suffering from atopic dermatitis, 5 bp-allergic patients suffering from rhinoconjunctivitis only, 5 patients with respiratory allergy without bp allergy and 5 non-allergic individuals...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894001/intestinal-type-1-regulatory-t-cells-migrate-to-periphery-to-suppress-diabetogenic-t-cells-and-prevent-diabetes-development
#18
Hua Yu, Nicola Gagliani, Harumichi Ishigame, Samuel Huber, Shu Zhu, Enric Esplugues, Kevan C Herold, Li Wen, Richard A Flavell
Growing insight into the pathogenesis of autoimmune diseases and numerous studies in preclinical models highlights the potential of regulatory T cells to restore tolerance. By using non-obese diabetic (NOD) BDC2.5 TCR-transgenic (Tg), and IL-10 and Foxp3 double-reporter mice, we demonstrate that alteration of gut microbiota during cohousing experiments or treatment with anti-CD3 mAb significantly increase intestinal IL-10-producing type 1 regulatory T (Tr1) cells and decrease diabetes incidence. These intestinal antigen-specific Tr1 cells have the ability to migrate to the periphery via a variety of chemokine receptors such as CCR4, CCR5, and CCR7 and to suppress proliferation of Th1 cells in the pancreas...
September 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28875388/intrinsic-renal-cells-induce-lymphocytosis-of-th22-cells-from-iga-nephropathy-patients-through-b7-ctla-4-and-ccl-ccr-pathways
#19
Lu Gan, Qiaoling Zhou, Xiaozhao Li, Chen Chen, Ting Meng, Jiaxi Pu, Mengyuan Zhu, Chenggen Xiao
IgA nephropathy (IgAN), the most common glomerulonephritis, has an unclear pathogenesis. The role of Th22 cells, which are intimately related to proteinuria and progression in IgAN, in mediating infection-related IgAN is unclear. This study aimed to characterize the association between intrinsic renal cells (tubular epithelial cells and mesangial cells) and Th22 cells in immune regulation of infection-related IgAN and to elucidate the impact of Th22 lymphocytosis; the proinflammatory cytokines IL-1, IL-6, and TNF-α; and CCL chemokines on kidney fibrosis...
September 5, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28870639/migratory-properties-of-ex-vivo-expanded-regulatory-t-cells-influence-of-all-trans-retinoic-acid-and-rapamycin
#20
J L Beermann, C T Thiesler, U Dringenberg, C Alter, S Kuhs, S Velaga, S N Ukena, A Franzke
Adoptively transferred regulatory T-cells represent a promising therapeutic approach for tolerance induction in autoimmunity and transplantation medicine. However, a major hurdle for clinical application is the manufacturing of sufficient Treg cell numbers with respect to the low frequency of naturally occurring Tregs in the peripheral blood. Therefore, ex vivo large-scale expansion is mandatory for most of the clinical conditions. Besides the Treg cell number other parameters of the cell product are of high relevance for safe and efficient clinical Treg cell application like Treg cell purity, suppressive capacity and genetic stability of the Treg cell phenotype...
September 1, 2017: Transplant Immunology
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