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https://www.readbyqxmd.com/read/29771307/assessment-of-rosacea-symptom-severity-by-genome-wide-association-study-and-expression-analysis-highlights-immuno-inflammatory-and-skin-pigmentation-genes
#1
Jennifer L Aponte, Mathias N Chiano, Laura M Yerges-Armstrong, David A Hinds, Chao Tian, Akansha Gupta, Cong Guo, Dana J Fraser, Johannes M Freudenberg, Deepak K Rajpal, Margaret G Ehm, Dawn M Waterworth
Rosacea is a common, chronic skin disease of variable severity with limited treatment options. The cause of rosacea is unknown, but it is believed to be due to a combination of hereditary and environmental factors. Little is known about the genetics of the disease. We performed a genome-wide association study (GWAS) of rosacea symptom severity with data from 73,265 research participants of European ancestry from the 23andMe customer base. Seven loci had variants associated with rosacea at the genome-wide significance level (p≤5 × 10-8)...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29753029/inherited-genetic-variants-associated-with-melanoma-braf-nras-subtypes
#2
Nancy E Thomas, Sharon N Edmiston, Irene Orlow, Peter A Kanetsky, Li Luo, David C Gibbs, Eloise A Parrish, Honglin Hao, Klaus J Busam, Bruce K Armstrong, Anne Kricker, Anne E Cust, Hoda Anton-Culver, Stephen B Gruber, Richard P Gallagher, Roberto Zanetti, Stefano Rosso, Lidia Sacchetto, Terence Dwyer, David W Ollila, Colin B Begg, Marianne Berwick, Kathleen Conway
BRAF and NRAS mutations arise early in melanoma development but their associations with low-penetrance melanoma susceptibility loci remain unknown. In the Genes, Environment and Melanoma (GEM) Study, 1223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms (SNPs) identified as low-penetrant melanoma risk variants. We used multinomial logistic regression to simultaneously examine each SNP's relationship to BRAF V600E, BRAF V600K, BRAF other, and NRAS+ relative to BRAF-/NRAS- melanoma adjusted for study features...
May 9, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29752313/schistosomiasis-induces-persistent-dna-methylation-and-tuberculosis-specific-immune-changes
#3
Andrew R DiNardo, Tomoki Nishiguchi, Emily M Mace, Kimal Rajapakshe, Godwin Mtetwa, Alexander Kay, Gugu Maphalala, W Evan Secor, Rojelio Mejia, Jordan S Orange, Cristian Coarfa, Kapil N Bhalla, Edward A Graviss, Anna M Mandalakas, George Makedonas
Epigenetic mechanisms, such as DNA methylation, determine immune cell phenotype. To understand the epigenetic alterations induced by helminth coinfections, we evaluated the longitudinal effect of ascariasis and schistosomiasis infection on CD4+ T cell DNA methylation and the downstream tuberculosis (TB)-specific and bacillus Calmette-Guérin-induced immune phenotype. All experiments were performed on human primary immune cells from a longitudinal cohort of recently TB-exposed children. Compared with age-matched uninfected controls, children with active Schistosoma haematobium and Ascaris lumbricoides infection had 751 differentially DNA-methylated genes, with 72% hypermethylated...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29745988/differential-requirements-for-irf4-in-the-clonal-expansion-and-homeostatic-proliferation-of-naive-and-memory-murine-cd8-t-cells
#4
Mana Miyakoda, Kiri Honma, Daisuke Kimura, Masoud Akbari, Kazumi Kimura, Toshifumi Matsuyama, Katsuyuki Yui
Interferon regulatory factor 4 (IRF4) has critical roles in immune cell differentiation and function and is indispensable for clonal expansion and effector function in T cells. Here, we demonstrate that the AKT pathway is impaired in murine CD8+ T cells lacking IRF4. The expression of phosphatase and tensin homolog (PTEN), a negative regulator of the AKT pathway, was elevated in Irf4-/- CD8+ T cells. Inhibition of PTEN partially rescued downstream events, suggesting that PTEN constitutes a checkpoint in the IRF4-mediated regulation of cell signaling...
May 10, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29738359/genomic-profile-and-pathologic-features-of-diffuse-large-b-cell-lymphoma-subtype-of-methotrexate-associated-lymphoproliferative-disorder-in-rheumatoid-arthritis-patients
#5
Joaquim Carreras, Yara Yukie Kikuti, Masashi Miyaoka, Shinichiro Hiraiwa, Sakura Tomita, Haruka Ikoma, Yusuke Kondo, Sawako Shiraiwa, Kiyoshi Ando, Shinji Sato, Yasuo Suzuki, Ikuo Miura, Giovanna Roncador, Naoya Nakamura
Rheumatoid arthritis patients often develop the diffuse large B-cell lymphoma subtype of methotrexate-associated lymphoproliferative disorder (DLBCLMTX-LPD ). We characterized the genomic profile and pathologic characteristics of 20 biopsies using an integrative approach. DLBCLMTX-LPD was associated with extranodal involvement, a high/high-intermediate international prognostic index in 53% of cases, and responded to MTX withdrawal. The phenotype was nongerminal center B-cell in 85% of samples and Epstein-Barr encoding region positive (EBER+ ) in 65%, with a high proliferation index and intermediate MYC expression levels...
May 5, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29720240/integrative-analysis-reveals-cd38-as-a-therapeutic-target-for-plasma-cell-rich-pre-disease-and-established-rheumatoid-arthritis-and-systemic-lupus-erythematosus
#6
Suzanne Cole, Alice Walsh, Xuefeng Yin, Mihir D Wechalekar, Malcolm D Smith, Susanna M Proudman, Douglas J Veale, Ursula Fearon, Costantino Pitzalis, Frances Humby, Michele Bombardieri, Amy Axel, Homer Adams, Christopher Chiu, Michael Sharp, John Alvarez, Ian Anderson, Loui Madakamutil, Sunil Nagpal, Yanxia Guo
BACKGROUND: Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE. METHODS: RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target...
May 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29718735/expression-of-crbn-ikzf1-and-ikzf3-does-not-predict-lenalidomide-sensitivity-and-mutations-in-the-cereblon-pathway-are-infrequent-in-multiple-myeloma
#7
Konstantinos Dimopoulos, Helga Fibiger Munch-Petersen, Christian Winther Eskelund, Lene Dissing Sjö, Elisabeth Ralfkiaer, Peter Gimsing, Kirsten Grønbaek
The immunomodulatory drug thalidomide, and its analogs, lenalidomide, and pomalidomide (IMiDs), have become essential components of the standard treatment for multiple myeloma (MM), and have led to significant improvement of survival in patients with this devastating disease. Cereblon (CRBN), the direct target of IMiDs, has been proposed as a predictive biomarker of response to IMiDs. Using standard immunohistochemistry in formalin-fixed paraffin embedded (FFPE) bone marrow samples of 23 patients treated with a lenalidomide-containing regimen, we found that the malignant plasma cells of all the patients stained positive for CRBN, IKZF1, and IKZF3, regardless of sensitivity to IMiDs...
May 2, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29715623/weak-vaccinia-virus-induced-nk-cell-regulation-of-cd4-t-cells-is-associated-with-reduced-nk-cell-differentiation-and-cytolytic-activity
#8
Steven D Hatfield, Keith A Daniels, Carey L O'Donnell, Stephen N Waggoner, Raymond M Welsh
Natural killer (NK) cells control antiviral adaptive immune responses in mice during some virus infections, but the universality of this phenomenon remains unknown. Lymphocytic choriomeningitis virus (LCMV) infection of mice triggered potent cytotoxic activity of NK cells (NKLCMV ) against activated CD4 T cells, tumor cells, and allogeneic lymphocytes. In contrast, NK cells activated by vaccinia virus (VACV) infection (NKVACV ) exhibited weaker cytolytic activity against each of these target cells. Relative to NKLCMV cells, NKVACV cells exhibited a more immature (CD11b- CD27+ ) phenotype, and lower expression levels of the activation marker CD69, cytotoxic effector molecules (perforin, granzyme B), and the transcription factor IRF4...
April 28, 2018: Virology
https://www.readbyqxmd.com/read/29698503/gene-expression-profiles-of-immune-regulatory-genes-in-whole-blood-of-cattle-with-a-subclinical-infection-of-mycobacterium-avium-subsp-paratuberculosis
#9
Hyun-Eui Park, Hong-Tae Park, Young Hoon Jung, Han Sang Yoo
Johne's disease is a chronic wasting disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP), resulting in inflammation of intestines and persistent diarrhea. The initial host response against MAP infections is mainly regulated by the Th1 response, which is characterized by the production of IFN-γ. With the progression of disease, MAP can survive in the host through the evasion of the host's immune response by manipulating the host immune response. However, the host response during subclinical phases has not been fully understood...
2018: PloS One
https://www.readbyqxmd.com/read/29684346/microrna-3662-expression-correlates-with-antiviral-drug-resistance-in-adult-t-cell-leukemia-lymphoma-cells
#10
Kiyoshi Yasui, Mai Izumida, Takeya Nakagawa, Yoshinao Kubo, Hideki Hayashi, Takashi Ito, Hiroaki Ikeda, Toshifumi Matsuyama
Interferon regulatory factor (IRF) 4 and the proto-oncogene c-Rel cooperate in growth and antiviral drug resistance of adult T-cell leukemia/lymphoma (ATLL). To elucidate the target of IRF4 and c-Rel in ATLL, we determined the simultaneous binding sites of IRF4 and c-Rel using ChIP-seq technology. Nine genes were identified within 2 kb of binding sites, including MIR3662. Expression of miR-3662 was regulated by IRF4, and to a lesser extent by c-Rel. Cell proliferation was inhibited by knockdown of miR-3662 and expression of miR-3662 was correlated with antiviral drug resistance in ATLL cell lines...
April 20, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29676376/an-unusual-presentation-of-large-b-cell-lymphoma-with-interferon-regulatory-factor-4-gene-rearrangement
#11
Anuj Verma, Sridhar Epari, Sumeet Gujral, Tanuja Shet
Rearrangements involving interferon regulatory factor 4 (IRF4) gene has been recently described in a subtype of diffuse large B-cell lymphoma (DLBCL). They occur in a typical clinical setting of a pediatric age group, predominantly with tonsillar mass, usually as a low-stage disease and with good response to chemotherapy. Histomorphologically, they show nodular/follicular architecture with diffuse strong immunopositivity for multiple myeloma oncogene 1. Here, the authors describe one such unusual case of large B-cell lymphoma with IRF4 gene rearrangement in a young child with the unusual location of inguinal region and detailed pathological (histological, immunohistochemical, and molecular) findings...
April 2018: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29672174/th9-cells-probable-players-in-ulcerative-colitis-pathogenesis
#12
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/29669755/zinc-finger-irf-composite-elements-bound-by-ikaros-irf4-complexes-function-as-gene-repression-in-plasma-cell
#13
Kyoko Ochiai, Haruka Kondo, Yasunobu Okamura, Hiroki Shima, Yuko Kurokochi, Kazumi Kimura, Ryo Funayama, Takeshi Nagashima, Keiko Nakayama, Katsuyuki Yui, Kengo Kinoshita, Kazuhiko Igarashi
The transcription factor (TF) interferon regulatory factor-4 (IRF4) promotes both germinal center (GC) reactions and plasma cell (PC) differentiation by binding to alternative DNA motifs including AP-1-IRF composite elements, Ets-IRF composite elements (EICEs), and interferon sequence response elements (ISREs). Although all of these motifs mediate transcriptional activation by IRF4, it is still unknown how some of the IRF4 target genes are downregulated upon PC differentiation. Here, we revealed a molecular mechanism of IRF4-mediated gene downregulation during PC differentiation...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29669250/t-follicular-helper-cell-germinal-center-b-cell-interaction-strength-regulates-entry-into-plasma-cell-or-recycling-germinal-center-cell-fate
#14
Wataru Ise, Kentaro Fujii, Katsuyuki Shiroguchi, Ayako Ito, Kohei Kometani, Kiyoshi Takeda, Eiryo Kawakami, Kazuo Yamashita, Kazuhiro Suzuki, Takaharu Okada, Tomohiro Kurosaki
Higher- or lower-affinity germinal center (GC) B cells are directed either to plasma cell or GC recycling, respectively; however, how commitment to the plasma cell fate takes place is unclear. We found that a population of light zone (LZ) GC cells, Bcl6lo CD69hi expressing a transcription factor IRF4 and higher-affinity B cell receptors (BCRs) or Bcl6hi CD69hi with lower-affinity BCRs, favored the plasma cell or recycling GC cell fate, respectively. Mechanistically, CD40 acted as a dose-dependent regulator for Bcl6lo CD69hi cell formation...
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29669249/the-transcription-factor-runx3-establishes-chromatin-accessibility-of-cis-regulatory-landscapes-that-drive-memory-cytotoxic-t-lymphocyte-formation
#15
Dapeng Wang, Huitian Diao, Adam J Getzler, Walter Rogal, Megan A Frederick, Justin Milner, Bingfei Yu, Shane Crotty, Ananda W Goldrath, Matthew E Pipkin
T cell receptor (TCR) stimulation of naive CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naive cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 promoted accessibility to memory CTL-specific cis-regulatory regions before the first cell division and was essential for memory CTL differentiation. Runx3 was specifically required for accessibility to regions highly enriched with IRF, bZIP and Prdm1-like TF motifs, upregulation of TFs Irf4 and Blimp1, and activation of fundamental CTL attributes in early effector and memory precursor cells...
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29666157/cd30-expression-and-its-correlation-with-myc-and-bcl2-in-de-novo-diffuse-large-b-cell-lymphoma
#16
Qi-Xing Gong, Zhen Wang, Chong Liu, Xiao Li, Ting-Xun Lu, Jin-Hua Liang, Wei Xu, Jian-Yong Li, Zhi-Hong Zhang
AIM: CD30+ diffuse large B-cell lymphoma (DLBCL) has emerged as a new immunophenotypic variant of de novo DLBCLs. However, the prevalence of CD30 positivity is variable according to different studies, and the prognostic significance of CD30 is also controversial. This study aimed to investigate the positive expression rate and prognostic impact of CD30 in de novo DLBCLs and try to find the correlated influences. METHODS: A total of 241 patients with de novo DLBCL in east China from 2008 to 2015 were included to investigate the prevalence, clinicopathological features and outcomes of CD30+ de novo DLBCLs...
April 17, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29626160/nlrp3-regulates-macrophage-m2-polarization-through-up-regulation-of-il-4-in-asthma
#17
Ying Liu, Xin Gao, Yi Miao, Yuanyuan Wang, Huan Wang, Rui Zhang, Zhe Cheng, Xi Wang, Xiaogang Jing, Liuqun Jia, Lingling Dai, Meng Liu, Lin An
Activation of nucleotide binding oligomerization domain (Nod)-like receptor (NLR) protein 3 (NLRP3) inflammasome received substantial attention recently in inflammatory diseases. Macrophages contribute to allergic inflammation in asthma. This study was aimed to investigate the effect of NLRP3 inflammasome on the polarization of macrophages. We utilized human primary monocytes and monocyte-derived macrophages to study expression of NLRP3 inflammasome components (NLRP3, ASC, caspase-1) and its downstream cytokine interleukin-1β (IL-1β)...
April 6, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29622035/ccl17-blockade-as-a-therapy-for-osteoarthritis-pain-and-disease
#18
Ming-Chin Lee, Reem Saleh, Adrian Achuthan, Andrew J Fleetwood, Irmgard Förster, John A Hamilton, Andrew D Cook
BACKGROUND: Granulocyte macrophage-colony stimulating factor (GM-CSF) has been implicated in the pathogenesis of a number of inflammatory diseases and in osteoarthritis (OA). We identified previously a new GM-CSF→Jmjd3→interferon regulatory factor 4 (IRF4)→chemokine (c-c motif) ligand 17 (CCL17) pathway, which is important for the development of inflammatory arthritis pain and disease. Tumour necrosis factor (TNF) can also be linked with this pathway. Here we investigated the involvement of the pathway in OA pain and disease development using the GM-CSF-dependent collagenase-induced OA (CiOA) model...
April 5, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29616104/high-density-of-cd68-tumor-associated-macrophages-predicts-a-poor-prognosis-in-gastric-cancer-mediated-by-il-6-expression
#19
Chong-Yu Su, Xiao-Long Fu, Wei Duan, Pei-Wu Yu, Yong-Liang Zhao
The aim of the present study was to explore the potential role of cluster of differentiation CD68+ tumor-associated macrophages (TAMs) induced by interleukin (IL)-6 in the progression of gastric cancer (GC) and patient prognosis. The expression levels of IL-6 and CD68 were detected by immunohistochemical staining in 60 samples of tumor and non-tumor gastric tissues. CD14+ monocytes were isolated from peripheral blood mononuclear cells and stimulated with macrophage colony stimulation factor (M-CSF) and IL-6, and the expression levels of IL-10, IL-12, vascular endothelial growth factor (VEGF)-C and transforming growth factor (TGF)-β were measured by reverse transcription polymerase chain reaction and ELISA...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29616088/retrospective-screening-of-microarray-data-to-identify-candidate-ifn-inducible-genes-in-a-htlv-1-transformed-model
#20
Alaa Refaat, Mohamed Owis, Sherif Abdelhamed, Ikuo Saiki, Hiroaki Sakurai
HuT-102 cells are considered one of the most representable human T-lymphotropic virus 1 (HTLV-1)-infected cell lines for studying adult T-cell lymphoma (ATL). In our previous studies, genome-wide screening was performed using the GeneChip system with Human Genome Array U133 Plus 2.0 for transforming growth factor-β-activated kinase 1 (TAK1)-, interferon regulatory factor 3 (IRF3)- and IRF4-regulated genes to demonstrate the effects of interferon-inducible genes in HuT-102 cells. Our previous findings demonstrated that TAK1 induced interferon inducible genes via an IRF3-dependent pathway and that IRF4 has a counteracting effect...
April 2018: Oncology Letters
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