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Critical ilness

Ruben C Hoogeveen, Georg M Lauer
Kim and colleagues studied a large cohort of adults with acute symptomatic HAV infection. They found pervasive and profound CD8 T cell activation in the blood of these patients, together with increased T cell proliferation and expression of cytotoxic molecules in a substantial proportion and often the majority of circulating CD8 T cells. The degree of overall activation, proliferation and cytotoxic capacity was tightly correlated with liver damage, as measured by ALT serum levels. Critically, they showed that this activated CD8 T cell phenotype was not limited to HAV-specific T cells but was found on multiple HAV-unrelated specificities they tested, i...
August 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Na-Rae Lee, Ji-Yoon Choi, Il-Hee Yoon, Jong Kil Lee, Kyung-Soo Inn
Retinoic acid-inducible gene I (RIG-I) detects viral RNAs and induces antiviral responses. During viral RNA recognition by RIG-I, tripartite motif protein 25 (TRIM25) plays a critical regulatory role by inducing K63-linked RIG-I polyubiquitination. Previous proteomics analysis revealed several phosphorylation sites on TRIM25, including tyrosine 278 (Y278), yet the roles of these modifications remain elusive. Here, we demonstrated that TRIM25 interacted with c-Src and underwent tyrosine phosphorylation by c-Src kinase upon viral infection and the phosphorylation is required for the complete activation of RIG-I signaling...
August 7, 2018: Cellular Immunology
Agnes Jaeger-Lansky, Klara Schmidthaler, Lorenz Kuessel, Manuela Gstöttner, Petra Waidhofer-Söllner, Gerhard J Zlabinger, René Wenzl, Thomas Eiwegger
Endometriosis is a prevalent gynaecological disorder with a still unclear pathogenesis. So far inflammatory mechanisms are associated with disease progression and critical reviews have discussed the so-called 'danger theory' related to endometriosis. Hence, we performed immunoassays to evaluate whether local inflammation is linked to the severity of the disease. In addition, we investigated the role of recently described cytokines IL-33, IL-32α and the 'alarmin' high mobility group box 1 (HMGB1). We confirmed a dysfunctional immune response in the local environment of women suffering from endometriosis...
July 25, 2018: Journal of Reproductive Immunology
Sina Riemschneider, Janine Kohlschmidt, Christiane Fueldner, Charlotte Esser, Sunna Hauschildt, Jörg Lehmann
Intensive research during the past decade has highlighted the impact of the regulatory function of the aryl hydrocarbon receptor (AhR) in immunity. In this study, we focused on the influence of AhR activation on the differentiation of murine bone marrow-derived myeloid precursor cells into mature macrophages. Our results show that the activation of AhR by subtoxic doses of the AhR ligand benzo(a)pyrene (BaP) impaired the proliferation of bone marrow cells (BMCs) whereas the proportion of resulting adherent cells was not affected...
August 9, 2018: Toxicology Letters
Emily E Virgin, Kimberly A Rosvall
Immune function varies with an animal's endocrine physiology and energy reserves, as well as its abiotic and biotic environment. This context-dependency is thought to relate to adaptive trade-off resolution that varies from one context to the next; however, it is less clear how state- and environmentally-dependent differences in endocrine-immune signaling relate to survival in natural populations. We begin to address this question in a prospective study on a free-living passerine bird, the tree swallow (Tachycineta bicolor), by capitalizing upon naturally-occurring variation in ectoparasitism in 12-day old chicks...
August 9, 2018: General and Comparative Endocrinology
Seagal Teitz-Tennenbaum, Steven P Viglianti, Jonathan A Roussey, Stuart M Levitz, Michal A Olszewski, John J Osterholzer
The substantial morbidity and mortality caused by invasive fungal pathogens, including Cryptococcus neoformans , necessitates increased understanding of protective immune responses against these infections. Our previous work using murine models of cryptococcal lung infection demonstrated that dendritic cells (DCs) orchestrate critical transitions from innate to adaptive immunity and that IL-10 signaling blockade improves fungal clearance. To further understand interrelationships among IL-10 production, fungal clearance, and the effect of IL-10 on lung DCs, we performed a comparative temporal analysis of cryptococcal lung infection in wild type C57BL/6J mice (designated IL-10+/+ ) and IL-10-/- mice inoculated intratracheally with C...
August 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Jianping Shi, Shuixiu Li, Aili Gao, Kunju Zhu, Hong Zhang
BACKGROUND: Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the Chinese medicinal herb Stephaniae tetrandrae, has a long history in Chinese clinical applications as an anti-inflammatory or anti-arrhythmic agent in the treatment of diverse diseases. In our previous study, TET exhibited the synergisitic action on azoles against pathogenic fungi. PURPOSE: In the current study, we examined whether TET can enhance the antifungal activity of FLC against disseminated candidiasis in mice...
July 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Hong-Su Park, Guanqun Liu, Qiang Liu, Yan Zhou
Nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome plays a pivotal role in modulating lung inflammation in response to the influenza A virus infection. We previously showed that the swine influenza virus (SIV) infection induced NLRP3 inflammasome-mediated IL-1β production in primary porcine alveolar macrophages (PAMs), and we were interested in examining the upstream signaling events that are involved in this process. Here, we report that the SIV-infection led to dynamin-related protein 1 (DRP1) phosphorylation at serine 579 and mitochondrial fission in PAMs...
August 9, 2018: Viruses
Ke Su, Qian Zhao, Aiping Bian, Chunfang Wang, Yujie Cai, Yanyan Zhang
Long noncoding RNAs (lncRNAs), a novel class of transcripts that have critical roles in carcinogenesis and progression, have emerged as important gene expression modulators. However, the pathophysiological contributions and the underlying mechanisms of specific lncRNAs in cervical cancer remain largely unknown. Here, using transcriptome microarray analysis, we identified a novel lncRNA termed lncRNA upregulated in cervical cancer (lnc-UICC) that was highly expressed in cervical cancer tissue. lnc-UICC expression in cervical cancer was associated with FIGO stage, lymph node metastasis and prognosis...
2018: American Journal of Cancer Research
Xiaomei Chen, Peilong Lai, Yulian Wang, Chang He, Suijing Wu, Xin Huang, Suxia Geng, Chengwei Luo, Wei Ling, Lingji Zeng, Peng Li, Zhiwu Jiang, Jianyu Weng, Xin Du
Chronic graft-versus-host disease (cGVHD) manifests with features characteristic of autoimmune disease with organs attacked by pathogenic Th17 cells. However, the mechanism of Th17 cells generation in the setting of cGVHD is still unclear. Here we defined C5a/C5aR-IL-17Aaxis as a novel signaling that required in the pathologies of cGVHD. We firstly found a positive link between complement activation and the Th17 cells in patients with cGVHD. C5a, a critical component of complements, promoted the generation of Th17 cells in vitro and inhibition of the receptor for C5a (C5aR) reduced the Th17-bias response...
2018: American Journal of Translational Research
Aakanksha Jain, Ran Song, Edward K Wakeland, Chandrashekhar Pasare
Innate cytokines are critical drivers of priming and differentiation of naive CD4 T cells, but their functions in memory T cell response are largely undefined. Here we show that IL-1 acts as a licensing signal to permit effector cytokine production by pre-committed Th1 (IFN-γ), Th2 (IL-13, IL-4, and IL-5) and Th17 (IL-17A, IL-17F, and IL-22) lineage cells. This licensing function of IL-1 is conserved across effector CD4 T cells generated by diverse immunological insults. IL-1R signaling stabilizes cytokine transcripts to enable productive and rapid effector functions...
August 9, 2018: Nature Communications
Krystin Deason, Ty Dale Troutman, Aakanksha Jain, Dilip K Challa, Rajakumar Mandraju, Travis Brewer, E Sally Ward, Chandrashekhar Pasare
The toll-like receptor (TLR) and interleukin (IL)-1 family of receptors share several signaling components, including the most upstream adapter, MyD88. We previously reported the discovery of B cell adapter for phosphoinositide 3-kinase (BCAP) as a novel toll-IL-1 receptor homology domain-containing adapter that regulates inflammatory responses downstream of TLR signaling. Here we find that BCAP plays a critical role downstream of both IL-1 and IL-18 receptors to regulate T helper (Th) 17 and Th1 cell differentiation, respectively...
August 9, 2018: Journal of Experimental Medicine
Sarah K Whitley, Anand Balasubramani, Carlene Zindl, Ranjan Sen, Yoichiro Shibata, Gregory E Crawford, Nathaniel M Weathington, Robin D Hatton, Casey T Weaver
IL-1β plays a critical role in IL-6- and TGFβ- initiated Th17 differentiation and induction of Th17-mediated autoimmunity. However, the means by which IL-1 regulates various aspects of Th17 development remains poorly understood. We recently reported that IL-1β enhances STAT3 phosphorylation via NF-kB-mediated repression of SOCS3 to facilitate Il17 transcription and Th17 differentiation, identifying an effect of IL-1 signaling on proximal events of STAT3 signaling. Here we show that IL-1β promotes STAT3 binding to key cis-elements that control IL-17 expression...
August 9, 2018: Journal of Biological Chemistry
Tadafumi Fukata, Tsunekazu Mizushima, Junichi Nishimura, Daisuke Okuzaki, Xin Wu, Haruka Hirose, Yuhki Yokoyama, Yui Kubota, Kazuya Nagata, Naoto Tsujimura, Akira Inoue, Norikatsu Miyoshi, Naotsugu Haraguchi, Hidekazu Takahashi, Taishi Hata, Chu Matsuda, Hisako Kayama, Kiyoshi Takeda, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto
The incidence of inflammatory bowel disease (IBD) is increasing. Nucleic acid-based medicine has potential as a next-generation treatment, but it is rarely successful with IBD. The aim of this study was to establish a microRNA-based therapy in an IBD model. For this purpose, we used microRNA-29 (miR-29) and a supercarbonate apatite (sCA) nanoparticle as a drug delivery system. Injection of sCA-miR-29a-3p or sCA-miR-29b-3p into mouse tail veins markedly prevented and restored inflammation because of dextran sulfate sodium (DSS)-induced colitis...
August 6, 2018: Molecular Therapy. Nucleic Acids
Natalia Ziemkiewicz, Muhamed Talovic, Josh Madsen, Lindsay Hill, Robert Scheidt, Anjali Patel, Gabriel Haas, Madison Marcinczyk, Silviya Zustiak, Koyal Garg
Skeletal muscle has a remarkable regenerative capability following mild physical or chemical insult. However, following a critical loss of muscle tissue, the regeneration process is impaired due to the inadequate myogenic activity of muscle resident stem cells (i.e., satellite cells). Laminin (LM) is a heterotrimeric structural protein in the satellite cell niche that is crucial for maintaining its function. In this study, we created hydrogels composed of poly (ethylene glycol) (PEG) and LM-111 to provide an elastic substrate for satellite cell proliferation at the site of injury...
August 9, 2018: Biomedical Materials
Si Chen, Yuting Han, Hao Chen, Jing Wu, Min Zhang
PURPOSE: T helper (Th) 17 cells play a critical role in the development of asthma, but the underlying mechanism of how interleukin (IL)-17 is regulated in allergic airway inflammation is poorly understood. In this study, we investigated the impact of Bcl11b on Th17 response in asthma. METHODS: Blood samples from patients with mild asthma (MA) and severe asthma (SA) were collected. Expression of Bcl11b, IL-4, IL-5, IL-13, IL-17A and transforming growth factor (TGF)-β1 were determined in CD4⁺ T cells and plasma by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA)...
September 2018: Allergy, Asthma & Immunology Research
Seung Woon Rha, Seung Hyuk Choi, Doo Il Kim, Dong Woon Jeon, Jae Hwan Lee, Kyung Soon Hong, Tae Joon Cha, Jang Hyun Cho, Sang Kon Lee, Yong Hwan Park, Woo Jung Park, Hyun Joo Kim, Young Joo Kim, Juneyoung Lee, Donghoon Choi
BACKGROUND AND OBJECTIVES: We aimed to investigate the history of medical resource consumption and quality of life (QoL) in peripheral arterial disease (PAD) patients in Korea. METHODS: This was a prospective, multi-center (23 tertiary-hospitals, division of cardiology), non-interventional study. Adult patients (age ≥20 years) suffering from PAD for the last 12-month were enrolled in the study if they met with any of following; 1) ankle-brachial index (ABI) ≤0...
June 18, 2018: Korean Circulation Journal
Lyn M Wise, Gabriella S Stuart, Nicola C Real, Stephen B Fleming, Andrew A Mercer
Objective: Vascular endothelial growth factor (VEGF) family members are critical regulators of tissue repair and depending on their distinct pattern of receptor specificity can also promote inflammation and scarring. This study utilized a receptor-selective VEGF to examine the role of VEGF receptor (VEGFR)-2 in scar tissue (ST) formation. Approach: Cutaneous skin wounds were created in mice using a 4 mm biopsy punch and then treated until closure with purified VEGF-E derived from orf virus stain NZ-2. Tissue samples were harvested to measure gene expression using quantitative PCR and to observe ST formation through histological examination and changes in cell populations by immunofluorescence...
August 1, 2018: Advances in Wound Care
Hyeseon Cho, Henrique Jaime, Rafael Pires de Oliveira, Byunghyun Kang, Rosanne Spolski, Tina Vaziri, Timothy G Myers, Vishal Thovarai, Zeli Shen, James G Fox, Warren J Leonard, Brian L Kelsall
Despite studies indicating the effects of IL-21 signaling in intestinal inflammation, its roles in intestinal homeostasis and infection are not yet clear. Here, we report potent effects of commensal microbiota on the phenotypic manifestations of IL-21 receptor deficiency. IL-21 is produced highly in the small intestine and appears to be critical for mounting an IgA response against atypical commensals such as segmented filamentous bacteria and Helicobacter, but not to the majority of commensals. In the presence of these atypical commensals, IL-21R-deficient mice exhibit reduced numbers of germinal center and IgA+ B cells and expression of activation-induced cytidine deaminase in Peyer's patches as well as a significant decrease in small intestine IgA+ plasmablasts and plasma cells, leading to higher bacterial burdens and subsequent expansion of Th17 and Treg cells...
August 7, 2018: Mucosal Immunology
Jibin Li, Jian Xu, Xiaofei Yan, Keer Jin, Wenya Li, Rui Zhang
BACKGROUND Limited efficacy of immune checkpoint blockades was observed in clinical trials in colorectal (CRC) patients, especially in the microsatellite-stable patients. Interleukin-6 (IL-6) is critical in modeling immune responses in cancers. However, the effects of targeting IL-6 in combination with immune checkpoint blockades is unknown in CRC. MATERIAL AND METHODS In the present study, we investigated the profile of IL-6 expression in tumor tissues of CRC patient and we established CRC mouse models with various IL-6 expression levels using CT26 cells and MC38 cells...
August 8, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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