keyword
MENU ▼
Read by QxMD icon Read
search

rag1

keyword
https://www.readbyqxmd.com/read/28213501/immature-lymphocytes-inhibit-rag1-and-rag2-transcription-and-v-d-j-recombination-in-response-to-dna-double-strand-breaks
#1
Megan R Fisher, Adrian Rivera-Reyes, Noah B Bloch, David G Schatz, Craig H Bassing
Mammalian cells have evolved a common DNA damage response (DDR) that sustains cellular function, maintains genomic integrity, and suppresses malignant transformation. In pre-B cells, DNA double-strand breaks (DSBs) induced at Igκ loci by the Rag1/Rag2 (RAG) endonuclease engage this DDR to modulate transcription of genes that regulate lymphocyte-specific processes. We previously reported that RAG DSBs induced at one Igκ allele signal through the ataxia telangiectasia mutated (ATM) kinase to feedback-inhibit RAG expression and RAG cleavage of the other Igκ allele...
February 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28213473/central-role-of-t-helper-17-cells-in-chronic-hypoxia-induced-pulmonary-hypertension
#2
Levi D Maston, David T Jones, Wieslawa Giermakowska, Tamara A Howard, Judy L Cannon, Wei Wang, Yongyi Wei, Weimin Xuan, Thomas C Resta, Laura V Gonzalez Bosc
RATIONALE: Inflammation is a prominent pathologic feature in pulmonary arterial hypertension as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4(+) T cells are required for initiating and maintaining inflammation, suggesting these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28196762/enteric-helminth-induced-type-i-interferon-signalling-protects-against-pulmonary-virus-infection-through-interaction-with-the-microbiota
#3
Amanda J McFarlane, Henry J McSorley, Donald J Davidson, Paul M Fitch, Claire Errington, Karen J Mackenzie, Eva S Gollwitzer, Chris J C Johnston, Andrew S MacDonald, Michael R Edwards, Nicola L Harris, Benjamin J Marsland, Rick M Maizels, Jürgen Schwarze
BACKGROUND: Helminth parasites have been reported to have beneficial immune modulatory effects in allergic and autoimmune conditions and detrimental consequences in tuberculosis and some viral infections. Their role in co-infection with respiratory viruses is not clear. OBJECTIVE: Here, we investigated the effects of strictly enteric helminth infection with Heligmosomoides polygyrus on respiratory syncytial virus (RSV) infection in a mouse model. METHODS: A murine helminth/ RSV co-infection model was developed...
February 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28185879/ctla4-ig-effectively-controls-immune-activation-and-inflammatory-disease-in-a-novel-murine-model-of-leaky-scid
#4
Stéphanie Humblet-Baron, Susann Schönefeldt, Josselyn Garcia-Perez, Frédéric Baron, Emanuela Pasciuto, Adrian Liston
BACKGROUND: Severe combined immunodeficiency (SCID) can be caused by loss-of-function mutations in genes involved in the DNA recombination machinery, such as RAG1, RAG2 or DCLRE1C. Defective DNA recombination causes a developmental block in T cells and B cells, resulting in high susceptibility to infections. Hypomorphic mutations in the same genes can also give a partial loss of T cells, in a spectrum including leaky SCID (LS) and Omenn syndrome (OS). These patients not only develop life-threatening infections due to immunodeficiency, but also develop inflammatory/autoimmune conditions due to the presence of autoreactive T cells...
February 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28179379/rag1-2-induces-genomic-insertions-by-mobilizing-dna-into-rag1-2-independent-breaks
#5
Philipp C Rommel, Thiago Y Oliveira, Michel C Nussenzweig, Davide F Robbiani
The RAG recombinase (RAG1/2) plays an essential role in adaptive immunity by mediating V(D)J recombination in developing lymphocytes. In contrast, aberrant RAG1/2 activity promotes lymphocyte malignancies by causing chromosomal translocations and DNA deletions at cancer genes. RAG1/2 can also induce genomic DNA insertions by transposition and trans-V(D)J recombination, but only few such putative events have been documented in vivo. We used next-generation sequencing techniques to examine chromosomal rearrangements in primary murine B cells and discovered that RAG1/2 causes aberrant insertions by releasing cleaved antibody gene fragments that subsequently reintegrate into DNA breaks induced on a heterologous chromosome...
February 8, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28168393/enhanced-colorectal-cancer-metastases-in-the-alcohol-injured-liver
#6
Ashley M Mohr, John J Gould, Jacy L Kubik, Geoffrey A Talmon, Carol A Casey, Peter Thomas, Dean J Tuma, Benita L McVicker
Metastatic liver disease is a major cause of mortality in colorectal cancer (CRC) patients. Alcohol consumption is a noted risk factor for secondary cancers yet the role of alcoholic liver disease (ALD) in colorectal liver metastases (CRLM) is not defined. This work evaluated tumor cell colonization in the alcoholic host liver using a novel preclinical model of human CRC liver metastases. Immunocompromised Rag1-deficient mice were fed either ethanol (E) or isocaloric control (C) diets for 4 weeks prior to intrasplenic injection of LS174T human CRC cells...
February 6, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28166197/chemerin-has-a-protective-role-in-hepatocellular-carcinoma-by-inhibiting-the-expression-of-il-6-and-gm-csf-and-mdsc-accumulation
#7
Y Lin, X Yang, W Liu, B Li, W Yin, Y Shi, R He
Hepatocellular carcinoma (HCC) is linked to inflammation and immunosuppression. Chemerin is highly expressed in the liver and implicated in the regulation of inflammation. However, the role of chemerin in HCC remains unclear. In this study, we aimed to investigate whether chemerin is able to influence HCC progression by regulating tumor-associated inflammation. Here we demonstrated that chemerin significantly decreased in blood and tumor tissues of HCC patients, and tumor chemerin levels were inversely associated with the prognosis...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28137717/differentiated-state-of-initiating-tumor-cells-is-key-to-distinctive-immune-responses-seen-in-h-rasg12v-induced-squamous-tumors
#8
Michael A Podolsky, Jacob T Bailey, Andrew J Gunderson, Carrie J Oakes, Kyle Breech, Adam B Glick
Heterogeneity in tumor immune responses is a poorly understood yet critical parameter for successful immunotherapy. In two doxycycline-inducible models where oncogenic H-Ras(G12V) is targeted either to the epidermal basal/stem cell layer with a Keratin14-rtTA transgene (K14Ras), or committed progenitor/suprabasal cells with an Involucrin-tTA transgene (InvRas) we observed strikingly distinct tumor immune responses. On threshold doxycycline levels yielding similar Ras expression, tumor latency, and numbers, tumors from K14Ras mice had an immunosuppressed microenvironment while InvRas tumors had a pro-inflammatory microenvironment...
January 30, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28125560/o-012-il-36-signaling-controls-the-induced-regulatory-t-cell-th9-cell-balance-and-gut-inflammation
#9
Akihito Harusato, Hirohito Abo, Vu Ngo, Samuel Yi, Satoru Osuka, Jakob Kohlmeier, Jian-Dong Li, Andrew Gewirtz, Asma Nusrat, Timothy Denning
BACKGROUND: In the United States over 1.4 million people suffer from inflammatory bowel disease (IBD). Therefore, there is a pressing need for the development of novel molecular therapeutics targeting pro-inflammatory mediators. Recently a novel interleukin-1 family member, IL-36γ was shown to be up-regulated in patients with inflammatory bowel disease (IBD) and to play an important role in healing of acute intestinal damage in mice, however, the function of IL-36γ with regards to T helper (TH) cell differentiation during gut inflammation remains undefined...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28123544/molecular-heterogeneity-in-the-novel-fusion-gene-apip-fgfr2-diversity-of-genomic-breakpoints-in-gastric-cancer-with-high-level-amplifications-at-11p13-and-10q26
#10
Takashi Okuda, Tomohiko Taki, Kazuhiro Nishida, Yoshiaki Chinen, Hisao Nagoshi, Chouhei Sakakura, Masafumi Taniwaki
Several novel fusion transcripts were identified by next-generation sequencing in gastric cancer; however, the breakpoint junctions have yet to be characterized. The present study characterized a plethora of APIP-FGFR2 genomic breakpoints in the SNU-16 gastric cancer cell line, which harbored homogeneously staining regions (hsrs) and double minute chromosomes. Oligonucleotide microarrays revealed high-level amplifications at chromosomes 8q24.1 (0.8 Mb region), 10q26 (1.1 Mb) and 11p13 (1.1 Mb). These amplicons contained MYC and PVT1 at chromosome 8q24...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28115058/ccr6-is-dispensable-for-the-development-of-skin-lesions-induced-by-imiquimod-despite-its-effect-on-epidermal-homing-of-il-22-producing-cells
#11
Perrine M Cochez, Camille Michiels, Emilie Hendrickx, Nicolas Dauguet, Guy Warnier, Jean-Christophe Renauld, Laure Dumoutier
Expression of the chemokine receptor Ccr6 is shared by most IL-22 producing cells and Ccr6-deficient mice showed decreased IL-22 production and skin inflammation upon IL-23 intradermal injections. To determine whether this observation might be extended to another psoriasis model, we applied imiquimod on Ccr6-deficient mice. Whereas epidermal IL-22 production was decreased because of a deficient recruitment of γδ T cells in these mice, they were not protected against psoriatic lesions. When primary epidermis or dermis tissue culture cells from non-treated mice were stimulated ex vivo with IL-1α/IL-2/IL-23, we observed that Ccr6 is crucial for Il22 expression from epidermal but not dermal cultures...
January 20, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28109013/investigation-of-genetic-defects-in-severe-combined-immunodeficiency-patients-from-turkey-by-targeted-sequencing
#12
Baran Erman, Ivan Bilic, Tatjana Hirschmugl, Elisabeth Salzer, Heidrun Boztug, Özden Sanal, Deniz Çağdaş Ayvaz, Ilhan Tezcan, Kaan Boztug
Primary immunodeficiencies (PIDs) represent a large group of disorders with an increased susceptibility to infections. Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiencies (PIDs) with marked T-cell lymphopenia. Investigation of the genetic etiology using classical Sanger sequencing is associated with considerable diagnostic delay. We here established a custom-designed, next generation sequencing-based panel to efficiently identify disease-causing genetic defects in PID patients and applied this method in SCID patients of Turkish origin with previously undefined genetic etiology...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28108608/macrophage-proliferation-sustains-adipose-tissue-inflammation-in-formerly-obese-mice
#13
Brian F Zamarron, Taleen A Mergian, Kae Won Cho, Gabriel Martinez-Santibanez, Danny Luan, Kanakadurga Singer, Jennifer L DelProposto, Lynn M Geletka, Lindsey A Muir, Carey N Lumeng
Obesity causes dramatic proinflammatory changes in the adipose tissue immune environment, but relatively little is known regarding how this inflammation responds to weight loss (WL). To understand the mechanisms by which meta-inflammation resolves during WL, we examined adipose tissue leukocytes in mice after withdrawal of a high-fat diet. After 8 weeks of WL, mice achieved similar weights and glucose tolerance values as age-matched lean controls but showed abnormal insulin tolerance. Despite fat mass normalization, total and CD11c(+) adipose tissue macrophage (ATM) content remained elevated in WL mice for up to 6 months and was associated with persistent fibrosis in adipose tissue...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28087429/analysis-of-parameters-that-affect-human-hematopoietic-cell-outputs-in-mutant-c-kit-immunodeficient-mice
#14
Paul H Miller, Gabrielle Rabu, Margarita MacAldaz, David Jhf Knapp, Alice Ms Cheung, Kiran Dhillon, Naoto Nakamichi, Philip A Beer, Leonard D Shultz, R Keith Humphries, Connie J Eaves
Xenograft models are transforming our understanding of the output capabilities of primitive human hematopoietic cells in vivo. However, many variables that affect post-transplant reconstitution dynamics remain poorly understood. Here we show an equivalent level of human chimerism can be regenerated from human CD34(+) cord blood cells transplanted intravenously either with or without additional radiation-inactivated cells into 2-6 month-old NOD-Rag1(-/-)-IL2Rγc(-/-) (NRG) mice given a more radioprotective conditioning regimen than is possible in conventionally used, repair-deficient, NOD-Prkdc(scid/scid)-IL2Rγc(-/-) (NSG) hosts...
January 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28077655/expression-of-ifnlr1-on-intestinal-epithelial-cells-is-critical-to-the-antiviral-effects-of-ifn-lambda-against-norovirus-and-reovirus
#15
Megan T Baldridge, Sanghyun Lee, Judy J Brown, Nicole McAllister, Kelly Urbanek, Terence S Dermody, Timothy J Nice, Herbert W Virgin
: Interferon-lambda (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects are unclear. Here, we sought to identify IFN-λ responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1 We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28058717/deletional-tolerance-prevents-aqp4-directed-autoimmunity-in-mice
#16
Anna-Lena Vogel, Benjamin Knier, Katja Lammens, Sudhakar Reddy Kalluri, Tanja Kuhlmann, Jeffrey L Bennett, Thomas Korn
Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system (CNS) mediated by antibodies to the water channel protein AQP4 expressed in astrocytes. The contribution of AQP4-specific T cells to the class switch recombination of pathogenic AQP4-specific antibodies and the inflammation of the blood-brain barrier is incompletely understood, as immunogenic naturally processed T-cell epitopes of AQP4 are unknown. By immunizing Aqp4(-/-) mice with full-length murine AQP4 protein followed by recall with overlapping peptides, we here identify AQP4(201-220) as the major immunogenic IA(b) -restricted epitope of AQP4...
January 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28049044/lymphocytes-contribute-to-biliary-injury-and-fibrosis-in-experimental-xenobiotic-induced-cholestasis
#17
Nikita Joshi, Anna K Kopec, Holly Cline-Fedewa, James P Luyendyk
The etiology of chronic bile duct injury and fibrosis in patients with autoimmune cholestatic liver diseases is complex, and likely involves immune cells such as lymphocytes. However, most models of biliary fibrosis are not autoimmune in nature. Biliary fibrosis can be induced experimentally by prolonged exposure of mice to the bile duct toxicant alpha-naphthylisothiocyanate (ANIT). We determined whether lymphocytes contributed to ANIT-mediated biliary hyperplasia and fibrosis in mice. Hepatic accumulation of T-lymphocytes and increased serum levels of anti-nuclear-autoantibodies were evident in wild-type mice exposed to ANIT (0...
December 31, 2016: Toxicology
https://www.readbyqxmd.com/read/28039309/tissue-nonspecific-alkaline-phosphatase-expression-is-needed-for-the-full-stimulation-of-t-cells-and-t-cell-dependent-colitis
#18
Cristina Hernández-Chirlaque, Reyes Gámez-Belmonte, Borja Ocón, Patricia Martínez-Moya, Stefan Wirtz, Fermín Sánchez de Medina, Olga Martínez-Augustin
BACKGROUND AND AIMS: Two alkaline phosphatase isoforms, intestinal (IAP) and tissue non-specific alkaline phosphatase (TNAP), are coexpressed in mouse colon, with the latter predominating in colitis. We aimed to examine the role of TNAP in T lymphocytes using heterozygous TNAP(+/-) mice (as TNAP(-/-) mice are nonviable). METHODS: In vitro primary cultures and in vivo T cell models using TNAP(+/-) mice were used. RESULTS: Stimulated splenocytes (lipopolysaccharide and concanavalin A) and T lymphocytes (concanavalin A and a-CD3/a-CD28) showed a decreased cytokine production and expression when compared with WT cells...
December 30, 2016: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28034915/early-life-antibiotic-treatment-enhances-the-pathogenicity-of-cd4-t-cells-during-intestinal-inflammation
#19
Sebastian Scheer, Tiago S Medina, Alex Murison, Matthew D Taves, Frann Antignano, Alistair Chenery, Kiran K Soma, Georgia Perona-Wright, Mathieu Lupien, Cheryl H Arrowsmith, Daniel D De Carvalho, Colby Zaph
The incidence of inflammatory bowel diseases (IBDs) has steadily increased in recent decades-a phenomenon that cannot be explained by genetic mutations alone. Other factors, including the composition of the intestinal microbiome, are potentially important contributors to the increased occurrence of this group of diseases. Previous reports have shown a correlation between early-life antibiotic (Abx) treatment and an increased incidence of IBD. In this report, we investigated the effects of early-life Abx treatments on the pathogenicity of CD4(+) T cells using an experimental T cell transfer model of IBD...
December 29, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28031334/respiratory-influenza-virus-infection-induces-memory-like-liver-nk-cells-in-mice
#20
Tingting Li, Jian Wang, Yanshi Wang, Yongyan Chen, Haiming Wei, Rui Sun, Zhigang Tian
Although NK cells are classified as innate immune cells, recent studies have demonstrated the transformation of NK cells into long-lived memory cells that contribute to secondary immune responses in certain mouse models. However, whether NK cells mount an Ag-specific memory response to acute influenza virus infection has not yet been examined. Here, we show that, consistent with previous studies, lung NK cells play an important role in controlling viral proliferation after primary influenza virus infection...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
keyword
keyword
53438
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"