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https://www.readbyqxmd.com/read/28330900/adaptive-immune-responses-to-zika-virus-are-important-for-controlling-virus-infection-and-preventing-infection-in-brain-and-testes
#1
Clayton W Winkler, Lara M Myers, Tyson A Woods, Ronald J Messer, Aaron B Carmody, Kristin L McNally, Dana P Scott, Kim J Hasenkrug, Sonja M Best, Karin E Peterson
The recent association between Zika virus (ZIKV) and neurologic complications, including Guillain-Barré syndrome in adults and CNS abnormalities in fetuses, highlights the importance in understanding the immunological mechanisms controlling this emerging infection. Studies have indicated that ZIKV evades the human type I IFN response, suggesting a role for the adaptive immune response in resolving infection. However, the inability of ZIKV to antagonize the mouse IFN response renders the virus highly susceptible to circulating IFN in murine models...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28323052/multi-locus-phylogeny-reveals-instances-of-mitochondrial-introgression-and-unrecognized-diversity-in-kenyan-barbs-cyprininae-smiliogastrini
#2
Ray C Schmidt, Henry L Bart, Wanja Dorothy Nyingi
The phylogenetics and taxonomic status of small African barbs (Cyprininae: Smiliogastrini) remains unresolved despite the recent decision to elevate the genus name Enteromius for the group. The main barrier to understanding the origin of African small barbs and evolutionary relationships within the group is the poor resolution of phylogenies published to date. These phylogenies usually rely on mitochondrial markers and have limited taxon sampling. Here we investigate the phylogenetic relationships of small barbs of Kenya utilizing cytochrome b, Growth Hormone (GH) intron 2, and RAG1 markers from multiple populations of many species in the region...
March 18, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28322325/a-non-cell-autonomous-mouse-model-of-cns-haemangioblastoma-mediated-by-mutant-kras
#3
Leyuan Bao, Osama Al-Assar, Lesley F Drynan, Mark J Arends, Pam Tyers, Roger A Barker, Terence H Rabbitts
Haemangioblastoma is a rare malignancy of the CNS where vascular proliferation causes lesions due to endothelial propagation. We found that conditionally expressing mutant Kras, using Rag1-Cre, gave rise to CNS haemangioblastoma in the cortex and cerebellum in mice that present with highly vascular tumours with stromal cells similar to human haemangioblastomas. The aberrant haemangioblastoma endothelial cells do not express mutant Kras but rather the mutant oncogene is expressed in CNS interstitial cells, including neuronal cells and progeny...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28304369/the-role-of-adaptive-immunity-as-an-ecological-filter-on-the-gut-microbiota-in-zebrafish
#4
Keaton Stagaman, Adam R Burns, Karen Guillemin, Brendan Jm Bohannan
All animals live in intimate association with communities of microbes, collectively referred to as their microbiota. Certain host traits can influence which microbial taxa comprise the microbiota. One potentially important trait in vertebrate animals is the adaptive immune system, which has been hypothesized to act as an ecological filter, promoting the presence of some microbial taxa over others. Here we surveyed the intestinal microbiota of 68 wild-type zebrafish, with functional adaptive immunity, and 61 rag1(-) zebrafish, lacking functional B- and T-cell receptors, to test the role of adaptive immunity as an ecological filter on the intestinal microbiota...
March 17, 2017: ISME Journal
https://www.readbyqxmd.com/read/28266921/clinical-laboratory-and-molecular-findings-of-63-patients-with-severe-combined-immunodeficiency-a-decade%C3%A2-s-experience
#5
M R Fazlollahi, Z Pourpak, A A Hamidieh, M Movahedi, M Houshmand, M Badalzadeh, M Nourizadeh, M Mahloujirad, S Arshi, A M Nabavi, M Gharagozlou, A Khayatzadeh, A Dabbaghzade, L Atarod, F Zandieh, M Sadeghi Shabestary, M Mesdaghi, I Mohammadzadeh, S A Mahdaviani, M H Eslamian, F Pesaran, E Bahraminia, F Abolnezhadian, Z Arij, M Moin
BACKGROUND: Severe combined immunodeficiency (SCID) is known as a pediatric emergency disease with life threatening conditions. This is an exclusive report of clinical evaluation, immunological assessment, molecular analysis and outcomes of SCID patients in a tertiary referral center in Iran. METHODS: During January 2006 and December 2015, in a prospective cohort study, initial screening and advanced immunological tests were carried out on patients suspected of having SCID...
March 7, 2017: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/28246290/co-transplantation-of-mesenchymal-stem-cells-with-neonatal-porcine-islets-improve-graft-function-in-diabetic-mice
#6
Julie A Hayward, Cara E Ellis, Karen Seeberger, Timothy Lee, Bassem Salama, Aillette Mulet-Sierra, Purushothaman Kuppan, Adetola Adesida, Gregory S Korbutt
Mesenchymal stem cells (MSCs) possess immuno-regulatory, anti-inflammatory, and pro-angiogenic properties, and therefore have the potential to improve islet engraftment and survival. We assessed the effect human bone marrow derived MSCs have on neonatal porcine islets (NPIs) in vitro and determine islet engraftment and metabolic outcomes when co-transplanted in a mouse model. NPIs co-cultured with MSCs had greater cellular insulin content and increased glucose stimulate insulin secretion. NPIs were co-transplanted with or without MSCs in diabetic B6...
February 28, 2017: Diabetes
https://www.readbyqxmd.com/read/28246016/gut-specific-delivery-of-t-helper-17-cells-reduces-obesity-and-insulin-resistance-in-mice
#7
Chun-Pyo Hong, Areum Park, Bo-Gie Yang, Chang Ho Yun, Min-Jung Kwak, Gil-Woo Lee, Jung-Hwan Kim, Min Seong Jang, Eun-Jung Lee, Eun-Ji Jeun, Gihoon You, Kwang Soon Kim, Youngwoo Choi, Ji-Hwan Park, Daehee Hwang, Sin-Hyeog Im, Jihyun F Kim, Yoon-Keun Kim, Ju-Young Seoh, Charles D Surh, You-Me Kim, Myoung Ho Jang
BACKGROUND & AIMS: Obesity and metabolic syndrome have been associated with alterations to the intestinal microbiota. However, few studies examined the effects of obesity on the intestinal immune system. We investigated changes in subsets of intestinal CD4+ T-helper (Th) cells with obesity and the effects of gut-tropic Th17 cells in mice on a high-fat diet (HFD). METHODS: We isolated immune cells from small intestine and adipose tissue of C57BL/6 mice fed a normal chow diet or a HFD for 10 weeks and analyzed the cells by flow cytometry...
February 25, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28243233/zebra-fish-lacking-adaptive-immunity-acquire-an-antiviral-alert-state-characterized-by-upregulated-gene-expression-of-apoptosis-multigene-families-and-interferon-related-genes
#8
Pablo García-Valtanen, Alicia Martínez-López, Azucena López-Muñoz, Melissa Bello-Perez, Regla M Medina-Gali, María Del Mar Ortega-Villaizán, Monica Varela, Antonio Figueras, Víctoriano Mulero, Beatriz Novoa, Amparo Estepa, Julio Coll
To investigate fish innate immunity, we have conducted organ and cell immune-related transcriptomic as well as immunohistologic analysis in mutant zebra fish (Danio rerio) lacking adaptive immunity (rag1(-/-)) at different developmental stages (egg, larvae, and adult), before and after infection with spring viremia carp virus (SVCV). The results revealed that, compared to immunocompetent zebra fish (rag1(+/+) ), rag1(-/-) acquired increased resistance to SVCV with age, correlating with elevated transcript levels of immune genes in skin/fins and lymphoid organs (head kidney and spleen)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28216420/evaluation-of-rag1-mutations-in-an-adult-with-combined-immunodeficiency-and-progressive-multifocal-leukoencephalopathy
#9
Claudia Schröder, Niklas Thomas Baerlecken, Ulrich Pannicke, Thilo Dörk, Torsten Witte, Roland Jacobs, Matthias Stoll, Klaus Schwarz, Bodo Grimbacher, Reinhold E Schmidt, Faranaz Atschekzei
Here we describe novel mutations in recombination activation gene 1 (RAG1) in a compound heterozygous male patient with combined T and B cell immunodeficiency (CID). Clinical manifestations besides antibody deficiency included airway infections, granulomatosis and autoimmune features. He died at the age of 37 due to PML caused by JC virus infection. By targeted next-generation sequencing we detected post mortem in this patient three mutations in RAG1. One allele harbored two novel mutations (c.1123C>G, p...
February 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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
#10
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...
April 1, 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
#11
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
#12
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/cytotoxic-t-lymphocyte-associated-protein-4-ig-effectively-controls-immune-activation-and-inflammatory-disease-in-a-novel-murine-model-of-leaky-severe-combined-immunodeficiency
#13
Stéphanie Humblet-Baron, Susann Schönefeldt, Josselyn E Garcia-Perez, Frédéric Baron, Emanuela Pasciuto, Adrian Liston
BACKGROUND: Severe combined immunodeficiency can be caused by loss-of-function mutations in genes involved in the DNA recombination machinery, such as recombination-activating gene 1 (RAG1), RAG2, or DNA cross-link repair 1C (DCLRE1C). Defective DNA recombination causes a developmental block in T and B cells, resulting in high susceptibility to infections. Hypomorphic mutations in the same genes can also give rise to a partial loss of T cells in a spectrum including leaky severe combined immunodeficiency (LS) and Omenn syndrome (OS)...
February 7, 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
#14
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...
March 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28168393/enhanced-colorectal-cancer-metastases-in-the-alcohol-injured-liver
#15
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 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
#16
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-ras-g12v-induced-squamous-tumors
#17
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, whereas InvRas tumors had a proinflammatory microenvironment...
March 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
#18
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
#19
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%C3%A2-skin-lesions-induced-by-imiquimod-despite-its-effect-on-epidermal-homing-of%C3%A2-il-22-producing-cells
#20
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. Although 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 nontreated 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
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