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Susanne Bloch, Stephanie Zwicker, Nagihan Bostanci, Åsa Sjöling, Elisabeth A Boström, Georgios N Belibasakis, Christina Schäffer
The oral pathogen Tannerella forsythia possesses a unique surface (S-) layer with a complex O-glycan containing a bacterial sialic acid mimic in the form of either pseudaminic acid or legionaminic acid at its terminal position. We hypothesize that different T. forsythia strains employ these stereoisomeric sugar acids for interacting with the immune system and resident host tissues in the periodontium. Here, we show how T. forsythia strains ATCC 43037 and UB4, displaying pseudaminic acid and legionaminic acid, respectively, and selected cell surface mutants of these strains, modulate the immune response in monocytes and human oral keratinocytes (HOK) using a multiplex immunoassay...
December 12, 2017: Molecular Oral Microbiology
Hossam A Abdelsamed, Caitlin C Zebley, Ben Youngblood
Long-lived T-cell-mediated immunity requires persistence of memory T cells in an antigen-free environment while also maintaining a heightened capacity to recall effector functions. Such antigen-independent homeostatic proliferation is mediated in part by the common gamma-chain cytokines IL-7 and IL-15. To further explore the mechanisms governing maintenance of effector functions in long-lived memory T cells during antigen-independent proliferation, human naïve and memory CD8 T cells can be sorted from peripheral blood mononuclear cells (PBMCs), labeled with the proliferation-tracking dye carboxyfluorescein succinimidyl ester (CFSE), and then purified based on their levels of cell division...
November 20, 2017: Bio-protocol
Fabienne Venet, Guillaume Monneret
Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis can induce acute kidney injury and multiple organ failures and represents the most common cause of death in the intensive care unit. Sepsis initiates a complex immune response that varies over time, with the concomitant occurrence of both pro-inflammatory and anti-inflammatory mechanisms. As a result, most patients with sepsis rapidly display signs of profound immunosuppression, which is associated with deleterious consequences...
December 11, 2017: Nature Reviews. Nephrology
Chao Wang, Maria I Edilova, Lisa E Wagar, Shariq Mujib, Meromit Singer, Nicole F Bernard, Thérèse Croughs, Michael M Lederman, Irini Sereti, Margaret A Fischl, Elisabeth Kremmer, Mario Ostrowski, Jean-Pierre Routy, Tania H Watts
IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell counts after virologically successful antiretroviral therapy. IL-7 increases total circulating CD4 and CD8 T cell counts; however, its effect on HIV-specific CD8 T cells has not been fully examined. TRAF1, a prosurvival signaling adaptor required for 4-1BB-mediated costimulation, is lost from chronically stimulated virus-specific CD8 T cells with progression of HIV infection in humans and during chronic lymphocytic choriomeningitis infection in mice...
December 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Yongkui Wang, Min Xiao, Chen Tao, Jing Chen, Zhenyu Wang, Jun Yang, Zhenguo Chen, Zhipeng Zou, Anling Liu, Daozhang Cai, Yu Jiang, Changhai Ding, Mangmang Li, Xiaochun Bai
Osteoblasts provide a microenvironmental niche for B-cell commitment and maturation in the bone marrow (BM). Any abnormity of osteoblasts function may result in the defect of B lymphopoiesis. Signaling from mechanistic target of rapamycin complex 1 (mTORC1) has been implicated in regulating the expansion and differentiation of osteoblasts. Thus, we raise a hypothesis that mTORC1 signaling in osteoblasts plays a vital role in B-cell development. Inactivation of mTORC1 in osterix-expressing cells (mainly osteoblast lineage) through Osx-Cre-directed deletion of Raptor (an mTORC1-specific component) resulted in a reduction in the total B-cell population in the BM, which was due to a block in early B-cell development from the pro-B to pre-B cell stage...
December 5, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Cecile Le Saout, Megan A Luckey, Alejandro V Villarino, Mindy Smith, Rebecca B Hasley, Timothy G Myers, Hiromi Imamichi, Jung-Hyun Park, John J O'Shea, H Clifford Lane, Marta Catalfamo
IL-7 regulates homeostatic mechanisms that maintain the overall size of the T cell pool throughout life. We show that, under steady-state conditions, IL-7 signaling is principally mediated by activation of signal transducers and activators of transcription 5 (STAT5). In contrast, under lymphopenic conditions, there is a modulation of STAT1 expression resulting in an IL-7-dependent STAT1 and STAT5 activation. Consequently, the IL-7-induced transcriptome is altered with enrichment of IFN-stimulated genes (ISGs)...
November 16, 2017: JCI Insight
Pedro Lee, Rupali Gund, Abhik Dutta, Neha Pincha, Isha Rana, Subhasri Ghosh, Deborah Witherden, Eve Kandyba, Amanda MacLeod, Krzysztof Kobielak, Wendy L Havran, Colin Jamora
The cutaneous wound-healing program is a product of a complex interplay among diverse cell types within the skin. One fundamental process that is mediated by these reciprocal interactions is the mobilization of local stem cell pools to promote tissue regeneration and repair. Using the ablation of epidermal caspase-8 as a model of wound healing in Mus musculus, we analyzed the signaling components responsible for epithelial stem cell proliferation. We found that IL-1α and IL-7 secreted from keratinocytes work in tandem to expand the activated population of resident epidermal γδT-cells...
December 4, 2017: ELife
Arwen Stikvoort, Ahmed Gaballa, Martin Solders, Iris Nederlof, Björn Önfelt, Berit Sundberg, Mats Remberger, Mikael Sundin, Jonas Mattsson, Michael Uhlin
Acute graft-versus-host disease (aGVHD) is one of the main major complications of post hematopoietic stem cell transplantation (HSCT). Identifying patients at risk of severe aGVHD may lead to earlier intervention and treatment, resulting in increased survival and a better quality of life. We aimed to identify biomarkers in donor grafts and patient plasma around the time of transplantation which might be predictive of aGVHD development. We build upon our previously published methods by using multiplex assays and multi-colour flow cytometry...
November 29, 2017: Biology of Blood and Marrow Transplantation
Na-Ra Han, Phil-Dong Moon, Ka-Jung Ryu, Na-Rae Kim, Hyung-Min Kim, Hyun-Ja Jeong
Naringenin (NG) has various beneficial properties, such as anti-cancer and anti-inflammatory effects. Thymic stromal lymphopoietin (TSLP) induces mast cell proliferation and inflammatory reactions. The aim of this study was to investigate the regulatory effect of NG on TSLP-induced mast cell proliferation and inflammatory reactions using human mast cell line (HMC-1) cells. HMC-1 cells were pre-treated with NG and then treated with TSLP. HMC-1 cells proliferation was determined by quantifying bromodeoxyuridine incorporation...
November 29, 2017: Clinical and Experimental Pharmacology & Physiology
Jiao Yuan, Qiuyan Cui, Wei Tang, Chen Chao, Zhiguang Zhou, Lin Yang
To explore the type of cytokine (IL-2 or IL-7) and its most optimal concentration regarding the improvement of the signal-to-noise ratio of glutamic acid decarboxylase 65 (GAD65) in enzyme-linked immunospot (ELISPOT) assay in Type 1 diabetic (T1DM) patients.
 Methods: Twenty T1DM patients (Group A) and sixteen healthy controls matched with age and sex (Group B) were enrolled in our study, and their peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll method. GAD65, internal control and Pediacel served as "five-for-one" vaccine were selected as the stimulating antigen...
November 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Heng Zhang, Hao Yan, Jianzi Ying, Liqing Du, Chunze Zhang, Yiling Yang, Huaqing Wang, Hui Wang
Purpose- Ionizing radiation has been associated with adverse effects on the immune system. Currently, there are no effective treatment options to ameliorate these effects. The aim of the present study was to investigate the protective effects of resveratrol against radiation-induced long term immunosuppression in mice. Materials and methods- Mice were exposed to total body irradiation, and treated with resveratrol or vehicle. Several immune parameters were measured, including thymus and spleen weights, T lymphocyte and B lymphocyte count in peripheral blood, concanavalin A and lipopolysaccharide induced lymphocyte proliferation...
November 29, 2017: International Journal of Radiation Biology
Alanna C Green, Victoria Rudolph-Stringer, Andrew D Chantry, Joy Y Wu, Louise E Purton
Early B lymphopoiesis occurs in the bone marrow and is reliant on interactions with numerous cell types in the bone marrow microenvironment, particularly those of the mesenchymal lineage. Each cellular niche that supports the distinct stages of B lymphopoiesis is unique. Different cell types and signaling molecules are important for the progressive stages of B lymphocyte differentiation. Cells expressing CXCL12 and IL-7 have long been recognized as having essential roles in facilitating progression through stages of B lymphopoiesis...
November 26, 2017: Bone
Miles Berger, Vikram Ponnusamy, Nathaniel Greene, Mary Cooter, Jacob W Nadler, Allan Friedman, David L McDonagh, Daniel T Laskowitz, Mark F Newman, Leslie M Shaw, David S Warner, Joseph P Mathew, Michael L James
Introduction: Aside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. In vitro and mouse model studies suggest that propofol inhibits, while isoflurane increases, neuroinflammation. If these findings translate to humans, they could be clinically important since neuroinflammation has detrimental effects on neurocognitive function in numerous disease states. Materials and methods: To examine whether propofol and isoflurane differentially modulate neuroinflammation in humans, cytokines were measured in a secondary analysis of cerebrospinal fluid (CSF) samples from patients prospectively randomized to receive anesthetic maintenance with propofol vs...
2017: Frontiers in Immunology
Asuka Terashima
Sepsis is a systemic inflammatory response syndrome that occurs upon severe bacterial infection. Although the development of early treatment for sepsis improves the survival rate of sepsis patients, in the subacute phase, certain patients suffer from secondary infection due to immunosuppression. It has been reported that one of the causes of the immunocompromised state during sepsis is lymphopenia. However, the underlying mechanisms are not well understood. We found that acute inflammation induced the immunodeficiency caused by the reduction of the numbers of peripheral lymphocytes and common lymphoid progenitors(CLPs)in the bone marrow, which was associated with a dramatic decrease in the osteoblast number...
2017: Clinical Calcium
Jiyeon Yu, Seunga Choi, Hyeonkyeong Kim, Nari Lee, Hyeongseok Yun, Sumi Kim, Seong-Tae Jeong, Jaerang Rho
B lymphocytes are produced from hematopoietic stem cells (HSCs) through the highly ordered process of B lymphopoiesis, which is regulated by a complex network of cytokines, chemokines and cell adhesion molecules derived from the hematopoietic niche. Primary osteoblasts function as an osteoblastic niche (OBN) that supports in vitro B lymphopoiesis. However, there are significant limitations to the use of primary osteoblasts, including their relative scarcity and the consistency and efficiency of the limited purification and proliferation of these cells...
November 24, 2017: Experimental & Molecular Medicine
Morgan Yang, Yvonne Chung, Stephanie Lang, Nobuyo Yawata, Lay Leng Seah, Audrey Looi
PURPOSE: The primary aim of this study is to isolate cytokines specific for active Graves' orbitopathy (GO) in the tears of affected patients. The secondary aim is to identify other cytokines of interest and to look at the profile of their levels over time. METHODS: This is a prospective pilot study conducted at the Singapore National Eye Centre. A total of 10 patients with active GO and 10 patients from each of 3 control groups were recruited. The 3 control groups were the following: age-matched normal female patients, patients with GO who were clinically inactive and patients with bilateral viral conjunctivitis...
November 16, 2017: Endocrine
He Xu, Victoria A Bendersky, Todd V Brennan, Jaclyn R Espinosa, Allan D Kirk
Kidney transplant patients treated with belatacept without depletional induction experience higher rates of acute rejection compared to patients treated with conventional immunosuppression. Costimulation blockade-resistant rejection (CoBRR) is associated with terminally differentiated T cells. Alemtuzumab induction and belatacept/sirolimus immunotherapy effectively prevents CoBRR. We hypothesized that cells in late phases of differentiation would be selectively less capable of repopulating post-depletion than more naïve phenotypes, providing a potential mechanism by which lymphocyte depletion and repopulation could reduce the risk of CoBRR...
November 14, 2017: American Journal of Transplantation
Mei Yu, Yuhong Chen, Hu Zeng, Yongwei Zheng, Guoping Fu, Wen Zhu, Ulrich Broeckel, Praful Aggarwal, Amy Turner, Geoffrey Neale, Cliff Guy, Nan Zhu, Hongbo Chi, Renren Wen, Demin Wang
The precise molecular mechanism underlying the regulation of early B cell lymphopoiesis is unclear. The PLCγ signaling pathway is critical for antigen receptor-mediated lymphocyte activation, but its function in cytokine signaling is unknown. Here we show that PLCγ1/PLCγ2 double deficiency in mice blocks early B cell development at the pre-pro-B cell stage and renders B cell progenitors unresponsive to IL-7. PLCγ pathway inhibition blocks IL-7-induced activation of mTOR, but not Stat5. The PLCγ pathway activates mTOR through the DAG/PKC signaling branch, independent of the conventional Akt/TSC/Rheb signaling axis...
November 13, 2017: Nature Communications
Emily R Perito, Veeral Ajmera, Nathan M Bass, Philip Rosenthal, Joel E Lavine, Jeffrey B Schwimmer, Katherine P Yates, Anna Mae Diehl, Jean P Molleston, Karen F Murray, Ann Scheimann, Ryan Gill, David Glidden, Bradley Aouizerat
Background: Reliable non-invasive markers to characterize inflammation, hepatocellular ballooning, and fibrosis in nonalcoholic fatty liver disease (NAFLD) are lacking. We investigated the relationship between plasma cytokine levels and features of NAFLD histology to gain insight into cellular pathways driving NASH and to identify potential non-invasive discriminators of NAFLD severity and pattern. Methods: Cytokines were measured from plasma obtained at enrollment in pediatric participants in NASH Clinical Research Network studies with liver biopsy-proven NAFLD...
September 2017: Hepatology communications
Rosanne Spolski, Daniel Gromer, Warren J Leonard
Interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21 form a family of cytokines based on the sharing of a receptor component, the common cytokine receptor γ chain, γ c, which is encoded by the gene mutated in humans with X-linked severe combined immunodeficiency (XSCID). Together, these cytokines play critical roles in lymphoid development, differentiation, growth, and survival as well as mediating effector function. Here, we provide an overview of the main actions of members of this cytokine family but then primarily focus on IL-2 and IL-21, discussing their dynamic interplay and contributions to a fine-tuned immune response...
2017: F1000Research
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