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https://www.readbyqxmd.com/read/28437578/klrg1-impairs-treg-competitive-fitness-in-the-gut
#1
Holger Meinicke, Anna Bremser, Maria Brack, Klaudia Schrenk, Hanspeter Pircher, Ana Izcue
Immune homeostasis requires the tight, tissue-specific control of the different CD4(+) Foxp3(+) regulatory T cells (Treg) populations. The cadherin-binding inhibitory receptor KLRG1 is expressed by a subpopulation of Treg with GATA3(+) effector phenotype. Although such Treg are important for the immune balance, especially in the gut, the role of KLRG1 in Treg has not been assessed. Using KLRG1 KO mice, we found that KLRG1 deficiency does not affect Treg frequencies in spleen, mesenteric lymph nodes or intestine, or frequencies of GATA3(+) Treg in the gut...
April 24, 2017: Immunology
https://www.readbyqxmd.com/read/28437139/protection-against-common-bean-rust-conferred-by-a-gene-silencing-method
#2
Bret Cooper, Kimberly B Campbell
Rust disease of the dry bean plant, Phaseolus vulgaris, is caused by the fungus Uromyces appendiculatus. The fungus acquires its nutrients and energy from bean leaves using a specialized cell structure, the haustorium, through which it secretes effector proteins that contribute to pathogenicity by defeating the plant immune system. Candidate effectors have been identified by DNA sequencing and motif analysis, and some candidates have been observed in infected leaves by mass spectrometry. To assess their roles in pathogenicity, we have inserted small fragments of genes for five candidates into bean pod mottle virus...
April 24, 2017: Phytopathology
https://www.readbyqxmd.com/read/28437001/tumor-associated-changes-in-intestinal-epithelial-cells-cause-local-accumulation-of-klrg1-gata3-regulatory-t-cells-in-mice
#3
Holger Meinicke, Anna Bremser, Maria Brack, Paulina Akeus, Claire Pearson, Samuel Bullers, Katrin Hoffmeyer, Marc P Stemmler, Marianne Quiding-Järbrink, Ana Izcue
CD4(+) Foxp3(+) regulatory T cells (Treg) include differentiated populations of effector Treg characterized by the expression of specific transcription factors. Tumors, including intestinal malignancies, often present with local accumulation of Treg that can prevent tumor clearance, but how tumor progression leads to Treg accumulation is incompletely understood. Here using genetically modified mouse models we show that ablation of E-cadherin, a process associated with epithelial to mesenchymal transition (EMT) and tumor progression, promotes the accumulation of intestinal Treg by the specific accumulation of the KLRG1(+) GATA3(+) Treg subset...
April 24, 2017: Immunology
https://www.readbyqxmd.com/read/28436940/disruption-of-spatiotemporal-hypoxic-signaling-causes-congenital-heart-disease-in-mice
#4
Xuejun Yuan, Hui Qi, Xiang Li, Fan Wu, Jian Fang, Eva Bober, Gergana Dobreva, Yonggang Zhou, Thomas Braun
Congenital heart disease (CHD) represents the most prevalent inborn anomaly. Only a minority of CHD cases are attributed to genetic causes, suggesting a major role of environmental factors. Nonphysiological hypoxia during early pregnancy induces CHD, but the underlying reasons are unknown. Here, we have demonstrated that cells in the mouse heart tube are hypoxic, while cardiac progenitor cells (CPCs) expressing islet 1 (ISL1) in the secondary heart field (SHF) are normoxic. In ISL1+ CPCs, induction of hypoxic responses caused CHD by repressing Isl1 and activating NK2 homeobox 5 (Nkx2...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28436089/a-novel-dense-granule-protein-gra41-regulates-timing-of-egress-and-calcium-sensitivity-in-toxoplasma-gondii
#5
Kaice A LaFavers, Karla M Márquez-Nogueras, Isabelle Coppens, Silvia N J Moreno, Gustavo Arrizabalaga
Toxoplasma gondii is an obligate intracellular apicomplexan parasite with high seroprevalence in humans. Repeated lytic cycles of invasion, replication and egress drive both the propagation and the virulence of this parasite. Key steps in this cycle, including invasion and egress, depend on tightly regulated calcium fluxes and, while many of the calcium-dependent effectors have been identified, the factors that detect and regulate the calcium fluxes are mostly unknown. To address this knowledge gap, we used a forward genetic approach to isolate mutants resistant to extracellular exposure to the calcium ionophore A23187...
April 24, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28436029/wnt4-acts-downstream-of-bmp2-to-mediate-the-regulation-of-atra-signaling-on-runx1-expression-implications-for-terminal-differentiation-of-antler-chondrocytes
#6
Hong-Liang Zhang, Zhan-Qing Yang, Cui-Cui Duan, Shuang Geng, Kai Wang, Hai-Fan Yu, Zhan-Peng Yue, Bin Guo
Although ATRA is involved in regulating the proliferation and differentiation of chondrocytes, its underlying mechanism remains unknown. Here we showed that ATRA could stimulate the proliferation of antler chondrocytes and expression of COL X and MMP13 which were two well-known markers for hypertrophic chondrocytes. Silencing of CRABP2 prevented the induction of ATRA on chondrocyte terminal differentiation, while overexpression of CRABP2 exhibited the opposite effects. CYP26A1 and CYP26B1 weakened the sensitivity of antler chondrocytes to ATRA...
April 24, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28435841/evading-plant-immunity-feedback-control-of-the-t3ss-in-pseudomonas-syringae
#7
COMMENT
Christopher Waite, Jörg Schumacher, Milija Jovanovic, Mark Bennett, Martin Buck
Microbes are responsible for over 10% of the global yield losses in staple crops such as wheat, rice, and maize. Understanding the decision-making strategies that enable bacterial plant pathogens to evade the host immune system and cause disease is essential for managing their ever growing threat to food security. Many utilise the needle-like type III secretion system (T3SS) to suppress plant immunity, by injecting effector proteins that inhibit eukaryotic signalling pathways into the host cell cytoplasm. Plants can in turn evolve resistance to specific pathogens via recognition and blocking of the T3SS effectors, so leading to an ongoing co-evolutionary 'arms race' between pathogen and host pairs...
March 17, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28434980/thaw-and-use-target-cells-pre-labeled-with-calcein-am-for-antibody-dependent-cell-mediated-cytotoxicity-assays
#8
Shan Chung, Van Nguyen, Yuwen Linda Lin, Lynn Kamen, An Song
In vitro antibody-dependent cell-mediated cytotoxicity (ADCC) assays are routinely performed to support the research and development of therapeutic antibodies. In ADCC assays, target cells bound by the antibodies are lysed by activated effector cells following interactions between the Fc region of the bound antibody and Fcγ receptors on effector cells. Target cell lysis is typically measured by quantification of released endogenous enzymes, e.g., lactate dehydrogenase, or measurement of released exogenous labels, e...
April 20, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28434942/ipsc-derived-regulatory-dendritic-cells-inhibit-allograft-rejection-by%C3%A2-generating-alloantigen-specific-regulatory-t-cells
#9
Songjie Cai, Jiangang Hou, Masayuki Fujino, Qi Zhang, Naotsugu Ichimaru, Shiro Takahara, Ryoko Araki, Lina Lu, Ji-Mei Chen, Jian Zhuang, Ping Zhu, Xiao-Kang Li
Regulatory dendritic cell (DCregs)-based immunotherapy is a potential therapeutic tool for transplant rejection. We generated DCregs from murine induced pluripotent stem cells (iPSCs), which could remain in a "stable immature stage" even under strong stimulation. Harnessing this characteristic, we hypothesized that iPS-DCregs worked as a negative vaccine to generate regulatory T cells (Tregs), and induced donor-specific allograft acceptance. We immunized naive CBA (H-2K(k)) mice with B6 (H-2K(b)) iPS-DCregs and found that Tregs (CD4(+)CD25(+)FOXP3(+)) significantly increased in CBA splenocytes...
April 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28434702/inhibition-or-deletion-of-angiotensin-ii-type-1-receptor-suppresses-elastase-induced-experimental-abdominal-aortic-aneurysms
#10
Haojun Xuan, Baohui Xu, Wei Wang, Hiroki Tanaka, Naoki Fujimura, Masaaki Miyata, Sara A Michie, Ronald L Dalman
OBJECTIVE: Angiotensin (Ang) II type 1 receptor (AT1) activation is essential for the development of exogenous Ang II-induced abdominal aortic aneurysms (AAAs) in hyperlipidemic animals. Experimental data derived from this modeling system, however, provide limited insight into the role of endogenous Ang II in aneurysm pathogenesis. Consequently, the potential translational value of AT1 inhibition in clinical AAA disease management remains incompletely understood on the basis of the existing literature...
April 20, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28433699/egfr-mediated-apoptosis-via-stat3
#11
Nicole M Jackson, Brian P Ceresa
The Epidermal Growth Factor Receptor (EGFR) is a cell surface receptor with primary implications in cell growth in both normal and malignant tissue. Paradoxically, cell lines that hyperexpress the EGFR have been documented to undergo receptor-mediated apoptosis. The underlying mechanism by which EGF-induced apoptosis occurs however remains inexplicit. In an attempt to identify this mechanism, we assessed downstream effectors of EGFR in MDA-MB-468 cells during conditions of EGF-induced apoptosis. The effector assessment revealed STAT3 as a potential mediator of EGF-induced apoptosis...
April 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28433542/blockade-of-pdgf-receptors-by-crenolanib-has-therapeutic-effect-in-patient-fibroblasts-and-in-preclinical-models-of-systemic-sclerosis
#12
Katsunari Makino, Tomoko Makino, Lukasz Stawski, Julio C Mantero, Robert Lafyatis, Robert Simms, Maria Trojanowska
Systemic sclerosis (SSc) is a multi-organ fibrotic disease with few treatment options. Activated fibroblasts are the key effector cells in SSc responsible for the excessive production of collagen and the development of fibrosis. PDGF, a potent mitogen for cells of mesenchymal origin, has been implicated in the activation of SSc fibroblasts. Our aim was to examine the therapeutic potential of crenolanib, an inhibitor of PDGF receptor signaling, in cultured fibroblasts and in angiotensin II (Ang II)-induced skin and heart fibrosis...
April 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28433456/cytokine-alterations-and-cognitive-impairment-in-major-depressive-disorder-from-putative-mechanisms-to-novel-treatment-targets
#13
REVIEW
Błażej Misiak, Jan Aleksander Beszłej, Kamila Kotowicz, Monika Szewczuk-Bogusławska, Jerzy Samochowiec, Jolanta Kucharska-Mazur, Dorota Frydecka
Overwhelming evidence indicates the involvement of immune-inflammatory processes in the pathophysiology of major depressive disorder (MDD). Peripheral cytokine alterations serve as one of most consistently reported indices of subthreshold inflammatory state observed in MDD. Although cytokines cannot pass directly through the blood-brain barrier, a number of transport mechanisms have been reported. In addition, peripheral cytokines may impact central nervous system via downstream effectors of their biological activity...
April 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28433429/immunological-function-of-langerhans-cells-in-hiv-infection
#14
Takamitsu Matsuzawa, Youichi Ogawa, Kohji Moriishi, Shinji Shimada, Tatsuyoshi Kawamura
BACKGROUND: Langerhans cells (LCs) are one of the initial target cells for HIV following sexual exposure and they are productively infected by HIV. HIV-infected LCs migrate to the draining lymph nodes (dLNs) and transmit the virus to CD4(+) T cells, leading to the dissemination of HIV. In contrast with the role of LCs in initial HIV acquisition, little is known about the modulation of immune responses by HIV-infected LCs. OBJECTIVE: We aimed to elucidate the induction of HIV-specific CD8(+) T cells and regulatory T cells (Tregs), both of which play important roles in regulating the progression of HIV infection...
April 9, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28433198/tumor-promoting-role-of-anti-tumor-macrophages-in-tumor-microenvironment
#15
REVIEW
Kuntal Kanti Goswami, Tithi Ghosh, Sarbari Ghosh, Madhurima Sarkar, Anamika Bose, Rathindranath Baral
Recent advances in tumor biology demand detailed analysis of the complex interaction of tumor cells with their adjacent microenvironment (tumor stroma) to understand the various mechanisms involved in tumor growth and metastasis. Mononuclear phagocytes or macrophages, a type of innate immune cells, defend the organism against infection and injury. On the otherhand, tumor associated macrophages (TAMs) constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype...
April 13, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28432872/human-effector-memory-t-helper-cells-engage-with-mouse-macrophages-and-cause-graft-versus-host-like-pathology-in-skin-of-humanized-mice-used-in-a-nonclinical-immunization-study
#16
Bala S Sundarasetty, Valery Volk, Sebastian J Theobald, Susanne Rittinghausen, Dirk Schaudien, Vanessa Neuhaus, Constanca Figueiredo, Andreas Schneider, Laura Gerasch, Adele Mucci, Thomas Moritz, Constantin von Kaisenberg, Loukia M Spineli, Katherina Sewald, Armin Braun, Henning Weigt, Arnold Ganser, Renata Stripecke
Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4(+) T cells in peripheral blood and lymph nodes...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28432554/epigallocatechin-gallate-protects-beas-2b-cells-from-lipopolysaccharide-induced-apoptosis-through-upregulation-of-gastrin-releasing-peptide
#17
Peethambaran Divya, Bijesh Puthusseri, Denny Joseph Kollareth Manual, Mohammed Azharuddin Savanur
Gastrin-releasing peptide (GRP) plays a major role in the development and maintenance of lung epithelial cells by promoting cell division, whereas its suppression causes growth arrest and apoptosis. The present study shows that human bronchial epithelial BEAS-2B cells challenged with lipopolysaccharide (LPS), an endotoxin from gram-negative bacteria, downregulated GRP expression and induced apoptosis via upregulation of p53 and active caspase-3, signifying the importance of GRP in lung epithelial cell survival...
April 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28432456/deregulated-bcl-2-family-proteins-impact-on-repair-of-dna-double-strand-breaks-and-are-targets-to-overcome-radioresistance-in-lung-cancer
#18
Sarah A Wieczorek, Frank Breitenbuecher, Aashish Soni, Katja Paul-Konietzko, Sophie Ziegler, Ali Sak, George Iliakis, Martin Schuler
PURPOSE: DNA damage-induced cell death is a major effector mechanism of radiotherapy. Aberrant expression of anti-apoptotic BCL-2 family proteins is frequently observed in lung cancers. Against this background, we studied radioresistance mediated by BCL-2 family proteins at the mechanistic level and its potential as target for radiochemotherapy. METHODS: Lung cancer models stably expressing BCL-xL or MCL-1 were irradiated to study cell death, clonogenic survival, and DNA repair kinetics in vitro, and growth suppression of established tumors in vivo...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28432378/advances-in-anti-viral-immune-defence-revealing-the-importance-of-the-ifn-jak-stat-pathway
#19
REVIEW
Nicola Raftery, Nigel J Stevenson
Interferon-alpha (IFN-α) is a potent anti-viral cytokine, critical to the host immune response against viruses. IFN-α is first produced upon viral detection by pathogen recognition receptors. Following its expression, IFN-α embarks upon a complex downstream signalling cascade called the JAK/STAT pathway. This signalling pathway results in the expression of hundreds of effector genes known as interferon stimulated genes (ISGs). These genes are the basis for an elaborate effector mechanism and ultimately, the clearance of viral infection...
April 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28432358/differential-sensitivity-to-infections-and-antimicrobial-peptide-mediated-immune-response-in-four-silkworm-strains-with-different-geographical-origin
#20
Ottavia Romoli, Alessio Saviane, Andrea Bozzato, Paola D'Antona, Gianluca Tettamanti, Andrea Squartini, Silvia Cappellozza, Federica Sandrelli
The domesticated silkworm Bombyx mori has an innate immune system, whose main effectors are the antimicrobial peptides (AMPs). Silkworm strains are commonly grouped into four geographical types (Japanese, Chinese, European and Tropical) and are generally characterised by a variable susceptibility to infections. To clarify the genetic and molecular mechanisms on which the different responses to infections are based, we exposed one silkworm strain for each geographical area to oral infections with the silkworm pathogens Enterococcus mundtii or Serratia marcescens...
April 21, 2017: Scientific Reports
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