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https://www.readbyqxmd.com/read/29444188/switching-and-loss-of-cellular-cytokine-producing-capacity-characterize-in-vivo-viral-infection-and-malignant-transformation-in-human-t-lymphotropic-virus-type-1-infection
#1
Huseini Kagdi, Maria Antonietta Demontis, Juan Carlos Ramos, Graham P Taylor
Adult T-cell leukaemia/lymphoma (ATL) arises from chronic non-malignant human T lymphotropic virus type-1 (HTLV-1) infection which is characterized by high plasma pro-inflammatory cytokines whereas ATL is characterized by high plasma anti-inflammatory (IL-10) concentrations. The poor prognosis of ATL is partly ascribed to disease-associated immune suppression. ATL cells have a CD4+CCR4+CD26-CD7- immunophenotype but infected cells with this immunophenotype ('ATL-like' cells) are also present in non-malignant HTLV-1 infection...
February 14, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29438013/the-ccr4-not-deadenylase-complex-controls-atg7-dependent-cell-death-and-heart-function
#2
Tomokazu Yamaguchi, Takashi Suzuki, Teruki Sato, Akinori Takahashi, Hiroyuki Watanabe, Ayumi Kadowaki, Miyuki Natsui, Hideaki Inagaki, Satoko Arakawa, Shinji Nakaoka, Yukio Koizumi, Shinsuke Seki, Shungo Adachi, Akira Fukao, Toshinobu Fujiwara, Tohru Natsume, Akinori Kimura, Masaaki Komatsu, Shigeomi Shimizu, Hiroshi Ito, Yutaka Suzuki, Josef M Penninger, Tadashi Yamamoto, Yumiko Imai, Keiji Kuba
Shortening and removal of the polyadenylate [poly(A)] tail of mRNA, a process called deadenylation, is a key step in mRNA decay that is mediated through the CCR4-NOT (carbon catabolite repression 4-negative on TATA-less) complex. In our investigation of the regulation of mRNA deadenylation in the heart, we found that this complex was required to prevent cell death. Conditional deletion of the CCR4-NOT complex components Cnot1 or Cnot3 resulted in the formation of autophagic vacuoles and cardiomyocyte death, leading to lethal heart failure accompanied by long QT intervals...
February 6, 2018: Science Signaling
https://www.readbyqxmd.com/read/29434669/copy-number-variation-and-regions-of-homozygosity-analysis-in-patients-with-m%C3%A3-llerian-aplasia
#3
Durkadin Demir Eksi, Yiping Shen, Munire Erman, Lynn P Chorich, Megan E Sullivan, Meric Bilekdemir, Elanur Yılmaz, Guven Luleci, Hyung-Goo Kim, Ozgul M Alper, Lawrence C Layman
Background: Little is known about the genetic contribution to Müllerian aplasia, better known to patients as Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Mutations in two genes (WNT4 and HNF1B) account for a small number of patients, but heterozygous copy number variants (CNVs) have been described. However, the significance of these CNVs in the pathogenesis of MRKH is unknown, but suggests possible autosomal dominant inheritance. We are not aware of CNV studies in consanguineous patients, which could pinpoint genes important in autosomal recessive MRKH...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29414279/mogamulizumab-anti-ccr4-in-htlv-1-associated-myelopathy
#4
Tomoo Sato, Ariella L G Coler-Reilly, Naoko Yagishita, Natsumi Araya, Eisuke Inoue, Rie Furuta, Toshiki Watanabe, Kaoru Uchimaru, Masao Matsuoka, Naoki Matsumoto, Yasuhiro Hasegawa, Yoshihisa Yamano
BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) causes the debilitating neuroinflammatory disease HTLV-1-associated myelopathy-tropical spastic paraparesis (HAM-TSP) as well as adult T-cell leukemia-lymphoma (ATLL). In patients with HAM-TSP, HTLV-1 infects mainly CCR4+ T cells and induces functional changes, ultimately causing chronic spinal cord inflammation. We evaluated mogamulizumab, a humanized anti-CCR4 monoclonal antibody that targets infected cells, in patients with HAM-TSP...
February 8, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29399406/deep-sequencing-of-the-t-cell-receptor-visualizes-reconstitution-of-t-cell-immunity-in-mogamulizumab-treated-adult-t-cell-leukemia
#5
Takero Shindo, Kazutaka Kitaura, Hiroshi Ureshino, Kazuharu Kamachi, Masaharu Miyahara, Kazuko Doi, Tatsuro Watanabe, Eisaburo Sueoka, Tadasu Shin-I, Ryuji Suzuki, Shinya Kimura
Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4+ regulatory T cells. We previously showed that next generation sequencing enables precise analysis of the T cell receptor (TCR) repertoire, and we here used the technique to reveal the immunological dynamics in moga-treated ATL patients...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29397397/nanos-genes-and-their-role-in-development-and-beyond
#6
REVIEW
Evi De Keuckelaere, Paco Hulpiau, Yvan Saeys, Geert Berx, Frans van Roy
The hallmark of Nanos proteins is their typical (CCHC)2 zinc finger motif (zf-nanos). Animals have one to four nanos genes. For example, the fruit fly and demosponge have only one nanos gene, zebrafish and humans have three, and Fugu rubripes has four. Nanos genes are mainly known for their evolutionarily preserved role in germ cell survival and pluripotency. Nanos proteins have been reported to bind the C-terminal RNA-binding domain of Pumilio to form a post-transcriptional repressor complex. Several observations point to a link between the miRNA-mediated repression complex and the Nanos/Pumilio complex...
February 3, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29395067/high-density-proximity-mapping-reveals-the-subcellular-organization-of-mrna-associated-granules-and-bodies
#7
Ji-Young Youn, Wade H Dunham, Seo Jung Hong, James D R Knight, Mikhail Bashkurov, Ginny I Chen, Halil Bagci, Bhavisha Rathod, Graham MacLeod, Simon W M Eng, Stéphane Angers, Quaid Morris, Marc Fabian, Jean-François Côté, Anne-Claude Gingras
mRNA processing, transport, translation, and ultimately degradation involve a series of dedicated protein complexes that often assemble into large membraneless structures such as stress granules (SGs) and processing bodies (PBs). Here, systematic in vivo proximity-dependent biotinylation (BioID) analysis of 119 human proteins associated with different aspects of mRNA biology uncovers 7424 unique proximity interactions with 1,792 proteins. Classical bait-prey analysis reveals connections of hundreds of proteins to distinct mRNA-associated processes or complexes, including the splicing and transcriptional elongation machineries (protein phosphatase 4) and the CCR4-NOT deadenylase complex (CEP85, RNF219, and KIAA0355)...
February 1, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29371324/outcomes-of-patients-with-relapsed-aggressive-adult-t-cell-leukemia-lymphoma-clinical-effectiveness-of-anti-ccr4-antibody-and-allogeneic-hematopoietic-stem-cell-transplantation
#8
Shigeo Fuji, Atae Utsunomiya, Yoshitaka Inoue, Takashi Miyagi, Satsuki Owatari, Yasushi Sawayama, Yukiyoshi Moriuchi, Ilseung Choi, Takero Shindo, Shin-Ichiro Yoshida, Satoshi Yamasaki, Takuhiro Yamaguchi, Takahiro Fukuda
No abstract text is available yet for this article.
January 25, 2018: Haematologica
https://www.readbyqxmd.com/read/29365477/association-between-blood-levels-of-ccr4-expressing-t-helper-cells-chemokine-ccl17-and-severity-of-coronary-atherosclerosis
#9
Alexandr Karpov, Anna Rvacheva, Maryana Shogenova, Radima Merova, Vladimir Naumov, Masenko Valerij
No abstract text is available yet for this article.
August 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29361236/%C3%AE-arrestin-2-dependent-signaling-promotes-ccr4-mediated-chemotaxis-of-murine-t-helper-type-2-cells
#10
Rui Lin, Yeon Ho Choi, David A Zidar, Julia K L Walker
Allergic asthma is a complex inflammatory disease that leads to significant healthcare costs and reduction in quality of life. Although many cell types are implicated in the pathogenesis of asthma, CD4+ T helper type 2 cells (Th2) are centrally involved. We previously reported that the asthma phenotype is virtually absent in ovalbumin-sensitized and -challenged mice that lack global expression of βarrestin-2 and that CD4+ T cells from these mice displayed significantly reduced C-C motif chemokine 22 (CCL22)-mediated chemotaxis...
January 23, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29341283/mogamulizumab-induced-photosensitivity-in-patients-with-mycosis-fungoides-and-other-t-cell-neoplasms
#11
Y Masuda, K Tatsuno, S Kitano, H Miyazawa, J Ishibe, M Aoshima, T Shimauchi, T Fujiyama, T Ito, Y Tokura
BACKGROUND: Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4 and was first approved in Japan for the treatment of adult T-cell leukaemia/lymphoma (ATLL), followed by cutaneous T-cell lymphoma and peripheral T-cell lymphoma. OBJECTIVE: To retrospectively investigate development of photosensitivity in patients with mycosis fungoides and other T-cell neoplasms after treatment with Mog. METHODS: We treated seven cutaneous lymphoma patients with Mog...
January 16, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29338773/chemokine-ligand-receptor-interactions-critically-regulate-cutaneous-wound-healing
#12
Erich Bünemann, Norman-Philipp Hoff, Bettina Alexandra Buhren, Ulrike Wiesner, Stephan Meller, Edwin Bölke, Anja Müller-Homey, Robert Kubitza, Thomas Ruzicka, Albert Zlotnik, Bernhard Homey, Peter Arne Gerber
BACKGROUND: Wound healing represents a dynamic process involving directional migration of different cell types. Chemokines, a family of chemoattractive proteins, have been suggested to be key players in cell-to-cell communication and essential for directed migration of structural cells. Today, the role of the chemokine network in cutaneous wound healing is not fully understood. Unraveling the chemokine-driven communication pathways in this complex process could possibly lead to new therapeutic strategies in wound healing disorders...
January 16, 2018: European Journal of Medical Research
https://www.readbyqxmd.com/read/29331522/nanos3-not-nanos1-and-nanos2-is-a-germ-cell-marker-gene-in-large-yellow-croaker-during-embryogenesis
#13
Kunhuang Han, Shihai Chen, Mingyi Cai, Yonghua Jiang, Ziping Zhang, Yilei Wang
In this study, three nanos gene subtypes (Lcnanos1, Lcnanos2 and Lcnanos3) from Larimichthys crocea, were cloned and characterized. We determined the spatio-temporal expression patterns of each subtype in tissues as well as the cellular localization of mRNA in embryos. Results showed that deduced Nanos proteins have two main homology domains: N-terminal CCR4/NOT1 deadenylase interaction domain and highly conserved carboxy-terminal region bearing two conserved CCHC zinc-finger motifs. The expression levels of Lcnanos1 in testis were significantly higher than other tissues, followed by heart, brain, eye, and ovary...
January 10, 2018: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29327377/s%C3%A3-zary-syndrome-managed-with-histone-deacetylase-inhibitor-followed-by-anti-ccr4-monoclonal-antibody
#14
T Numata, T Nagatani, K Shirai, T Maeda, K Mae, M Nakasu, M Saito, T Usuda, R Tsuboi, Y Okubo
A 70-year-old man presented to our clinic with a 10-year history of recurrent pruritic erythema and plaques on his trunk and limbs. Based on the pathological findings and monoclonal rearrangement of the T-cell receptor (TCR)-Cβ1 gene, mycosis fungoides (T2N0M0B0 stage IB) was diagnosed. Despite combination therapy including histone deacetylase inhibitor (vorinostat), the symptoms slowly evolved into Sézary syndrome (SS; T4N1M0B2) over 4 years, with dense infiltrates due to atypical lymphocytes expressing CCR4 developing in the entire dermis...
January 12, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29309794/minimally-invasive-skin-tape-strip-rna-seq-identifies-novel-characteristics-of-type-2-high-atopic-dermatitis-disease-endotype
#15
Nathan Dyjack, Elena Goleva, Cydney Rios, Byung Eui Kim, Lianghua Bin, Patricia Taylor, Caroline Bronchick, Clifton F Hall, Brittany N Richers, Max A Seibold, Donald Y Leung
BACKGROUND: Expression profiling of skin biopsies has established molecular features of the skin in atopic dermatitis (AD). Invasiveness of biopsies has prevented their use in defining individual level AD pathobiological mechanisms (endotypes) in large research studies. OBJECTIVE: To determine if minimally invasive skin tape strip transcriptome analysis identifies gene expression dysregulation in AD and molecular disease endotypes. METHODS: We sampled non-lesional and lesional skin tape strips and biopsies from adult Caucasian subjects AD patients (18 males, 12 females; age (Mean±SE) 36...
January 5, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29309749/patients-with-idiopathic-endplate-inflammation-displayed-aberrant-th17-responses-resulting-in-proinflammatory-monocyte-activation
#16
Jian Wang, Wanju Sun, Allen Bond, Chengpin Xu, Kai Li, Donglin Ren, Xin Song, Fang Tan, Kun Jiao, Mingfei Wang
Endplate inflammation remains a difficult task to diagnose and treat, partly due to the absence of in-depth understanding of the cellular and molecular factors driving this condition. In the current study, we investigated the circulating immune cells in patients with idiopathic endplate inflammation. Compared to healthy controls, the patients with endplate inflammation presented a significant upregulation of Th17 cells, characterized by higher frequencies of circulating IL-17+CD4+ T cells examined directly ex vivo and after PMA and ionomycin (PMA/I) stimulation...
January 5, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29298770/mogamulizumab-tops-standard-of-care-for-ctcl
#17
(no author information available yet)
In the large international phase III MAVORIC trial, patients with previously treated cutaneous T-cell lymphoma who received the anti-CCR4 monoclonal antibody mogamulizumab experienced significantly longer progression-free survival and higher response rates, as well as better quality of life, than those who received vorinostat, a standard therapy.
January 3, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29291391/tryptophan-mediated-interactions-between-tristetraprolin-and-the-cnot9-subunit-are-required-for-ccr4-not-deadenylase-complex-recruitment
#18
D Bulbrook, H Brazier, P Mahajan, M Kliszczak, O Fedorov, F P Marchese, A Aubareda, R Chalk, S Picaud, C Strain-Damerell, P Filippakopoulos, O Gileadi, A R Clark, W W Yue, N A Burgess-Brown, J L E Dean
The zinc-finger protein tristetraprolin (TTP) binds to AU-rich elements present in the 3' untranslated regions of transcripts that mainly encode proteins of the inflammatory response. TTP-bound mRNAs are targeted for destruction via recruitment of the eight-subunit deadenylase complex 'carbon catabolite repressor protein 4 (CCR4) -negative on TATA-less (NOT)' which catalyzes the removal of mRNA poly-(A) tails, the first obligatory step in mRNA decay. Here we show that a novel interaction between TTP and the CCR4-NOT subunit, CNOT9, is required for recruitment of the deadenylase complex...
December 29, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29289977/anti-pd-1-induced-high-grade-hepatitis-associated-with-corticosteroid-resistant-t-cells-a-case-report
#19
Helen M McGuire, Elena Shklovskaya, Jarem Edwards, Paul R Trevillian, Geoffrey W McCaughan, Patrick Bertolino, Catriona McKenzie, Ralph Gourlay, Stuart J Gallagher, Barbara Fazekas de St Groth, Peter Hersey
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control...
December 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29287991/t-cell-phenotypes-in-women-with-chlamydia-trachomatis-infection-and-influence-of-treatment-on-phenotype-distributions
#20
Brian M O Ogendi, Rakesh K Bakshi, Kanupriya Gupta, Richa Kapil, LaDraka T Brown, Stephen J Jordan, Steffanie Sabbaj, Christen G Press, Jeannette Y Lee, William M Geisler
T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38+HLA-DR+), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3+CCR5+ and CCR4+, respectively), and T cell homing marker (CCR7) for both CD4+ and CD8+ T cells in CT-infected women...
December 26, 2017: Microbes and Infection
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