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Keiko Aota, Tomoko Yamanoi, Koichi Kani, Koh-Ichi Nakashiro, Naozumi Ishimaru, Masayuki Azuma
BACKGROUND: Mechanisms underlying immune cells' recruitment and activation into the inflammatory lesions of lip salivary glands (LSGs) from primary Sjögren's syndrome (pSS) patients are incompletely understood. Chemokines play pivotal roles in these processes, so we investigated the clinical significance of chemokine receptor CXCR3 and its ligands in the autoimmune lesions of pSS. METHODS: We histologically determined the grade of LSG samples from 22 pSS patients and subjected the samples to immunofluorescence analysis to determine the expressions of CXCR3 and its ligands: CXCL9, CXCL10, and CXCL11...
June 21, 2018: Journal of Oral Pathology & Medicine
Deepak Kaul, Deepti Malik, Sameena Wani
Cross-talk between coding RNAs and regulatory non-coding microRNAs, within human genome, has provided compelling evidence for the existence of flexible checkpoint control of T-Cell activation. The present study attempts to demonstrate that the interplay between miR-2909 and its effector KLF4 gene has the inherent capacity to regulate genes coding for CTLA4, CD28, CD40, CD134, PDL1, CD80, CD86, IL-6 and IL-10 within normal human peripheral blood mononuclear cells (PBMCs). Based upon these findings, we propose a pathway that links miR-2909 RNomics with the genes coding for immune checkpoint regulators required for the maintenance of immune homeostasis...
June 20, 2018: Molecular and Cellular Biochemistry
Ta Sun, Fanqi Wang, Wen Pan, Qihan Wu, Jingwen Wang, Jianfeng Dai
Ticks, blood-feeding arthropods, and secrete immunosuppressive molecules that inhibit host immune responses and provide survival advantages to pathogens. In this study, we characterized the immunosuppressive function of a novel tick salivary protein, DsCystatin, from Dermacentor silvarum of China. DsCystatin directly interacted with human Cathepsins L and B and inhibited their enzymatic activities. DsCystatin impaired the expression of inflammatory cytokines such as IL1β, IFNγ, TNFα, and IL6 from mouse bone marrow-derived macrophages (BMDMs) that had been stimulated with LPS or Borrelia burgdorferi ...
2018: Frontiers in Immunology
Francesco Ursini, Emilio Russo, Roberto De Giorgio, Giovambattista De Sarro, Salvatore D'Angelo
Psoriatic arthritis (PsA) is a chronic inflammatory disease of joints, tendon sheaths, and entheses affecting patients with established skin psoriasis, or, less frequently, patients without a personal history of psoriasis with a positive familial history. Many treatment options are now available to deal with the different aspects of the disease, including traditional and biological disease-modifying antirheumatic drugs and the recently released targeted synthetic disease-modifying antirheumatic drugs. However, ~40% of patients still fail to achieve a meaningful clinical response to first-line biologic therapy advocating the development of novel medications...
2018: Therapeutics and Clinical Risk Management
Heng Dong, Zhi-Fa Wen, Lin Chen, Na Zhou, Hui Liu, Shiling Dong, Hong-Ming Hu, Yongbin Mou
Background: The aim of this study was to explore the feasibility of delivering tumor antigens and enhancing the antigen cross-presentation of dendritic cells (DCs) by aluminum hydroxide nanoparticle with polyethyleneimine (PEI) modification (LV@HPA/PEI). Materials and methods: The LV@HPA nanoparticles were modified by PEI first, then the influence of LV@HPA/PEI on DCs was examined. The distinct expression of ovalbumin (OVA) protein transported into DCs by LV@HPA/PEI was observed by flow cytometry and Western blot...
2018: International Journal of Nanomedicine
Dominika Polak, Christine Hafner, Peter Briza, Claudia Kitzmüller, Adelheid Elbe-Bürger, Nazanin Samadi, Maria Gschwandtner, Wolfgang Pfützner, Gerhard J Zlabinger, Beatrice Jahn-Schmid, Barbara Bohle
BACKGROUND: Neutrophils and allergen-specific T-cells accumulate in allergic late-phase reactions (LPR). Their presence is associated with severe inflammation. Cytokines like GM-CSF, IFN-γ, and IL-3, typically found in allergic LPR, have been proposed to convert neutrophils into antigen-presenting cells (APC). OBJECTIVE: To assess the antigen-processing and presenting capacity of neutrophils from allergic patients. METHODS: Neutrophils were isolated from peripheral blood of birch pollen-allergic donors and stimulated with GM-CSF, IFN-γ, and IL-3...
June 16, 2018: Journal of Allergy and Clinical Immunology
Hiromi Shiratori, Carmen Feinweber, Sonja Luckhardt, Nadja Wallner, Gerd Geisslinger, Andreas Weigert, Michael J Parnham
Macrophages undergo activation by pathophysiological stimuli to pro-inflammatory and bactericidal, or wound-healing and anti-inflammatory phenotypes, termed M1 or M2, respectively. Dysregulation of the M1-M2 balance is often associated with inflammatory diseases. Therefore, mechanisms of macrophage polarization may reveal new drug targets. We profiled six compounds with claimed modulatory effects on macrophage polarization using peripheral blood monocyte-derived macrophages. Based on the distinct mRNA or protein expression in macrophages stimulated either with M1 [lipopolysaccharide (LPS) + interferon-γ, IFNγ] or M2 interleukin-4 (IL-4) stimuli, we selected a combination of M1 (IL1β, tumor necrosis factor-α,TNFα, CC chemokine receptor 7, CCR7 and CD80) and M2 (chemokine (C-C motif) ligand 22, CCL22, CD200R and mannose receptor C type 1, MRC1) markers to monitor drug effects on "M1 polarization" or cells "pre-polarized to M1"...
June 16, 2018: European Journal of Pharmacology
Sharmeen Nishat, Leah M Wuescher, Randall G Worth
Staphylococcus aureus is a major human pathogen that can cause mild to severe life threatening infections in many tissues and organs. Platelets are known to participate in protection against S. aureus by directly killing and enhancing the activities of neutrophils and macrophages in clearing S. aureus infection. Platelets have also been shown to induce monocyte differentiation into dendritic cells and to enhance activation of dendritic cells. Therefore, in the present study, we explored the role of platelets in enhancing bone marrow derived dendritic cell (BMDC) function against S...
June 18, 2018: Infection and Immunity
Marlies Elderman, Floor Hugenholtz, Clara Belzer, Mark Boekschoten, Adriaan van Beek, Bart de Haan, Huub Savelkoul, Paul de Vos, Marijke Faas
BACKGROUND: A dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases. These diseases often show a sex bias, suggesting sex differences in immune responses and in the intestinal microbiome. We hypothesized that sex differences in immune responses are associated with sex differences in microbiota composition. METHODS: Fecal microbiota composition (MITchip), mRNA expression in intestinal tissue (microarray), and immune cell populations in mesenteric lymph nodes (MLNs) were studied in male and female mice of two mouse strains (C57B1/6OlaHsd and Balb/cOlaHsd)...
June 18, 2018: Biology of Sex Differences
Grasielle Pereira Jannuzzi, José Roberto Fogaça de Almeida, Suelen Silvana Dos Santos, Sandro Rogério de Almeida, Karen Spadari Ferreira
The Notch signaling pathway participates in several cellular functional aspects. This signaling has an important role in targeting both DC maturation and DC-mediated T cell responses. Thus, it is essential to investigate the influence of this signaling pathway in the role played by DCs in the pathogenesis of experimental paracoccidioidomycosis. This disease is a granulomatous and systemic mycosis that mainly affects lung tissue and can spread to any other organ and system. In this study, we demonstrated that bone marrow-derived DCs infected with yeasts from Paracoccidioides brasiliensis strain 18 performed efficiently their maturation after the activation of Notch signaling, with an increase in CD80, CD86, CCR7, and CD40 expression and the release of cytokines such as IL-6 and TNF-α...
June 18, 2018: Mycopathologia
Magdalena Kowalewicz-Kulbat, Piotr Szpakowski, Camille Locht, Franck Biet, Paulina Kaplonek, Krzysztof T Krawczyk, Joël Pestel, Wieslawa Rudnicka
Bacillus Calmette-Guérin (BCG) is the only vaccine available against tuberculosis and the tuberculin skin test (TST) is the most widely used method to detect BCG take. However, subjects may remain TST-negative, even after several BCG administrations. To investigate some of the potential reasons underlying this inability of developing tuberculin sensitivity in response to BCG we compared the effect of different mycobacterial stimuli in the groups differently responding to tuberculin. TST was performed on 71 healthy adults aged 25-30 years, who had received BCG in their childhood, and considered TST-positive at ≥10 mm...
June 13, 2018: Vaccine
Qiang Ma, Junning Liu, Guoliang Wu, Mujian Teng, Shaoxuan Wang, Meng Cui, Yuantao Li
Regulatory T (Treg) cells are critical suppressors of inflammation and are thought to exert mainly deleterious effects in cancers. In colorectal cancer (CRC), Foxp3+  Treg accumulation in the tumor was associated with poor prognosis. Hence, we examined the circulating Treg cells in CRC patients. Compared to controls, CRC patients presented mild upregulations in CD4+ CD25+/hi T cells and in the more canonical CD4+ CD25+/hi Foxp3+ Treg cells in peripheral blood mononuclear cells. Both of these Treg populations could be roughly divided into LAG3- TIM3- and LAG3+ TIM3+ subsets...
June 15, 2018: Clinical and Experimental Pharmacology & Physiology
Jorge Gallego-Valle, Verónica Astrid Pérez-Fernández, Rafael Correa-Rocha, Marjorie Pion
Regulatory B cells (Bregs) participate in auto-tolerance maintenance and immune homeostasis. Despite their impact on many diseases and due to the difficulty to define them, knowledge about their origin and their physiological inducers is still unclear. The incomplete understanding about the generation of Bregs and their limited numbers in periphery make it difficult to develop Breg-based therapy. Therefore, identifying factors that promote their development would allow their ex-vivo production in order to create new immunotherapy...
June 12, 2018: International Journal of Molecular Sciences
J Zheng, H Xue, H Zhang, L Wang, L Zheng, X Wang, X Lin, S Jin, J Wu
Hepatitis B virus (HBV) infection is a major public health problem and immune tolerance is responsible for persistent HBV infection. HBV therapeutic vaccines targeting HBV e antigen (HBeAg) may have an excellent effect in overcoming HBV immune tolerance. Thus, there is urgency for designing therapeutic vaccine candidates that target HBeAg. In this research, we fused the C (472-507) gene sequence of HBV with the extracellular domain of human CD40 ligand sequence and ligated this fused sequence into the pEGFP-N1 vector to construct the recombinant plasmid pEGFP-N1-C (472-507)-ecdCD40L...
2018: Acta Virologica
Ryutaro Iwabuchi, Shota Ikeno, Mie Kobayashi-Ishihara, Haruko Takeyama, Manabu Ato, Yasuko Tsunetsugu-Yokota, Kazutaka Terahara
Two cytokines, fms-related tyrosine kinase 3 ligand (Flt3-L) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are considered to be the essential regulators of dendritic cell (DC) development in vivo . However, the combined effect of Flt3-L and GM-CSF on human DCs has not been evaluated in vivo . In this study, we, therefore, aimed at evaluating this using a humanized mouse model. Humanized non-obese diabetic/SCID/Jak3null (hNOJ) mice were constructed by transplanting hematopoietic stem cells from human umbilical cord blood into newborn NOJ mice, and in vivo transfection (IVT) was performed by hydrodynamic injection-mediated gene delivery using plasmids encoding human Flt3-L and GM-CSF...
2018: Frontiers in Immunology
Rima Tapader, Dipro Bose, Pujarini Dutta, Santasabuj Das, Amit Pal
SslE (YghJ), a cell surface associated and secreted lipoprotein was identified as a potential vaccine candidate for extraintestinal pathogenic E. coli providing nearly complete protection from sepsis in a mouse model. We earlier found that SslE from neonatal septicemic E. coli could trigger the secretion of various proinflammatory cytokines in murine macrophages, the signaling pathway of which is still obscure. In this study, we showed that SslE specifically binds to TLR2/TLR1 heterodimer and recruits downstream adaptors MyD88, TIRAP and TRAF6...
June 11, 2018: Infection and Immunity
Amber J Giles, Marsha-Kay N D Hutchinson, Heather M Sonnemann, Jinkyu Jung, Peter E Fecci, Nivedita M Ratnam, Wei Zhang, Hua Song, Rolanda Bailey, Dionne Davis, Caitlin M Reid, Deric M Park, Mark R Gilbert
BACKGROUND: Corticosteroids are routinely utilized to alleviate edema in patients with intracranial lesions and are first-line agents to combat immune-related adverse events (irAEs) that arise with immune checkpoint blockade treatment. However, it is not known if or when corticosteroids can be administered without abrogating the efforts of immunotherapy. The purpose of this study was to evaluate the impact of dexamethasone on lymphocyte activation and proliferation during checkpoint blockade to provide guidance for corticosteroid use while immunotherapy is being implemented as a cancer treatment...
June 11, 2018: Journal for Immunotherapy of Cancer
Andrea Costantini, Nadia Viola, Antonella Berretta, Roberta Galeazzi, Giulia Matacchione, Jacopo Sabbatinelli, Gianluca Storci, Serena De Matteis, Luca Butini, Maria Rita Rippo, Antonio Domenico Procopio, Daniele Caraceni, Roberto Antonicelli, Fabiola Olivieri, Massimiliano Bonafè
Macrophage polarization is a candidate biomarker of disease-related inflammatory status, but its modulation during aging has not been investigated. To do this, the M1/M2 profile was assessed by CD80/CD163 gating in classical (CD14++ CD16- ), intermediate (CD14++ CD16+ ), and non-classical (CD14low CD16+ ) monocytes from 31 healthy subjects (CTRs) of different ages. Cytofluorimetric analysis showed a significantly different CD80/CD163 distribution in the three subsets, as more than 80% of classical and intermediate monocytes were CD80+ CD163+ , whereas most non-classical monocytes were CD80- CD163- and CD163+ ...
June 8, 2018: Aging
Piotr Orlowski, Emilia Tomaszewska, Katarzyna Ranoszek-Soliwoda, Marianna Gniadek, Olga Labedz, Tadeusz Malewski, Julita Nowakowska, Grzegorz Chodaczek, Grzegorz Celichowski, Jaroslaw Grobelny, Malgorzata Krzyzowska
Silver nanoparticles (AgNPs) are promising new antimicrobial agents against a wide range of skin and mucosal pathogens. However, their interaction with the immune system is currently not fully understood. Dendritic cells (DCs) are crucial during development of T cell-specific responses against bacterial and viral pathogens. We have previously shown that tannic acid-modified silver nanoparticles (TA-AgNPs) consist of a promising microbicide against HSV-2. The aim of this study was to compare the ability of TA-AgNPs or TA-AuNPs of similar sizes (TA-Ag/AuNPs) to induce DCs maturation and activation in the presence of HSV-2 antigens when used at non-toxic doses...
2018: Frontiers in Immunology
Apoorvi Chaudhri, Yanping Xiao, Alyssa N Klee, Xiaoxu Wang, Baogong Zhu, Gordon J Freeman
Programmed death ligand 1 (PD-L1)-mediated immune suppression regulates peripheral tolerance and is often co-opted by tumors to evade immune attack. PD-L1 binds to PD-1 but also binds to B7-1 (CD80) to regulate T-cell function. Binding interactions of PD-L1 with B7-1 and its functional role need further investigation to understand differences between PD-1 and PD-L1 tumor immunotherapy. We examined the molecular orientation of PD-L1 binding to B7-1 using cell-to-cell binding assays, ELISA, and flow cytometry...
June 5, 2018: Cancer Immunology Research
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