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Inderjit Singh, Devadoss J Samuvel, Seungho Choi, Nishant Saxena, Avtar K Singh, Jeseong Won
Recent studies report that loss and dysfunction of mitochondria and peroxisomes contribute to the myelin and axonal damage in multiple sclerosis (MS). In this study, we investigated the efficacy of lovastatin and AMPK activator (AICAR) combination on the loss and dysfunction of mitochondria and peroxisomes and myelin and axonal damage in the spinal cords, relative to the clinical disease symptoms, using a mouse model of experimental autoimmune encephalomyelitis (EAE, a model for MS). We observed that lovastatin and AICAR treatments individually provided partial protection of mitochondria/peroxisomes, myelin/axons, and thus partial attenuation of clinical disease in EAE mice...
January 13, 2018: Immunology
James A Giles, Andrew D Greenhalgh, Adam Denes, Bernhard Nieswandt, Graham Coutts, Barry W McColl, Stuart M Allan
Neutrophils are key components of the innate immune response, providing host defence against infection and being recruited to non-microbial injury sites. Platelets act as a trigger for neutrophil extravasation to inflammatory sites but mechanisms and tissue-specific aspects of these interactions are currently unclear. Here, we use bacterial endotoxin in mice to trigger an innate inflammatory response in different tissues and measure neutrophil invasion with or without platelet reduction. We show that platelets are essential for neutrophil infiltration to the brain, peritoneum and skin, neutrophil numbers returning to basal levels in the peritoneum and skin and being decreased (~60%) in the brain when platelets are reduced...
January 11, 2018: Immunology
Kazuhisa Furue, Takamichi Ito, Gaku Tsuji, Takafumi Kadono, Takeshi Nakahara, Masutaka Furue
Psoriasis is characterized by widespread scaly erythematous plaques that cause significant physical and psychological burdens for the affected individuals. Accelerated inflammation driven by the TNF-α/IL-23/IL-17 axis is now known to be the major mechanism of the development of psoriasis. In addition, psoriasis has an autoimmune nature that manifests as autoreactive T cells and is comorbid with other autoimmune diseases, such as autoimmune bullous diseases, vitiligo, alopecia and thyroiditis. In this article, we review the recent topics on autoimmunity and autoimmune comorbidities in psoriasis...
January 9, 2018: Immunology
Jacob V Gorman, John D Colgan
Tim-3 is a surface receptor expressed by Th1-type effector CD4 T cells, which are critical for defense against intracellular pathogens and have been implicated in autoimmune disease. Previous studies showed Tim-3 expression makes Th1 cells more susceptible to apoptosis and also marks functionally impaired T cells that arise due to chronic stimulation. However, other studies suggested Tim-3-expressing Th1 cells do not always have these properties. To further define the relationship between Tim-3 and Th1 cell function, we analyzed the characteristics of Th1 cells that expressed Tim-3 in response to brief stimulation in vitro or an acute viral infection in vivo...
January 9, 2018: Immunology
Kamilla Kjaergaard Jensen, Massimo Andreatta, Paolo Marcatili, Søren Buus, Jason A Greenbaum, Zhen Yan, Alessandro Sette, Bjoern Peters, Morten Nielsen
Major histocompatibility complex class II (MHC-II) molecules are expressed on the surface of professional antigen presenting cells where they display peptides to T helper cells, which orchestrate the onset and outcome of many host immune responses. Understanding which peptides will be presented by the MHC-II molecule is therefore important for understanding the activation of T helper cells and can be used to identify T-cell epitopes. We here present updated versions of two MHC class II peptide binding affinity prediction methods, NetMHCII and NetMHCIIpan...
January 6, 2018: Immunology
Matthew Collin, Venetia Bigley
Dendritic cells (DC) are a class of bone marrow derived cells arising from lympho-myeloid haematopoiesis that form an essential interface between the innate sensing of pathogens and the activation of adaptive immunity. This task requires a wide range of mechanisms and responses, which are divided between three major DC subsets: plasmacytoid DC (pDC), myeloid/conventional DC1 (cDC1) and myeloid/conventional DC2 (cDC2). Each DC subset develops under the control of a specific repertoire of transcription factors involving differential levels of IRF8 and IRF4 in collaboration with PU...
January 3, 2018: Immunology
Hilary A Seifert, Arthur A Vandenbark, Halina Offner
Current treatment options for human stroke are limited mainly to the modestly effective infusion of tissue plasminogen activator (tPA), with additional improvement of functional independence and higher rates of angiographic revascularization observed after mechanical thrombectomy. However, new therapeutic strategies that address post-stroke immune-mediated inflammatory responses are urgently needed. Recent studies in experimental stroke have firmly implicated immune mechanisms in the propagation and partial resolution of CNS damage after the ischemic event...
January 3, 2018: Immunology
Jinyong Choi, David Randall Pease, Siqi Chen, Bin Zhang, Hyewon Phee
The p21-activated kinase 2 (Pak2), an effector molecule of the Rho family GTPases Rac and Cdc42, regulates diverse functions of T cells. Previously, we showed that Pak2 is required for development and maturation of T cells in the thymus, including thymus-derived regulatory T cells (tTregs). However, whether Pak2 is required for functions of various subsets of peripheral T cells, such as naïve CD4 and helper T cell subsets including Foxp3+ regulatory T cells (Foxp3+Tregs), is unknown. To determine the role of Pak2 in CD4 T cells in the periphery, we generated inducible Pak2 knockout (KO) mice, in which Pak2 was deleted in CD4 T cells acutely by administration of tamoxifen...
January 3, 2018: Immunology
Barbara Bathke, Juliane Pätzold, Ronny Kassub, Raphael Giessel, Kerstin Lämmermann, Maria Hinterberger, Kay Brinkmann, Paul Chaplin, Mark Suter, Hubertus Hochrein, Henning Lauterbach
The immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen-presenting cells instruct T cells to expand and differentiate into effector and memory cells. Besides the essential stimulation of the T cell receptor complex a plethora of co-stimulatory signals not only ensures a proper T cell activation but also instils phenotypic and functional characteristics in the T cells appropriate to fight off the invading pathogen. The TNF receptor/ligand pair CD27/CD70 gained a lot of attraction due to its key role in regulating T cell activation, survival, differentiation, and maintenance, especially in the course of viral infections and cancer...
December 27, 2017: Immunology
Jason J Xenakis, Emily D Howard, Kalmia M Smith, Courtney L Olbrich, Yanjun Huang, Dilanjan Anketell, Samuel Maldonado, Evangeline W Cornwell, Lisa A Spencer
Intestinal eosinophils are implicated in homeostatic and disease-associated processes, yet the phenotype of intestinal tissue-dwelling eosinophils is poorly defined and their roles in intestinal health or disease remain enigmatic. Here we probed the phenotype and localization of eosinophils constitutively homed to the small intestine of naïve mice at baseline, and of antigen sensitized mice following intestinal challenge. Eosinophils homed to the intestinal lamina propria of naïve mice were phenotypically distinguished from autologous blood eosinophils, and constitutively expressed antigen presenting cell markers, suggesting intestinal eosinophils, unlike blood eosinophils, may be primed for antigen presentation...
December 27, 2017: Immunology
Clayton W Winkler, Karin E Peterson
Zika virus (ZIKV) is responsible for a recent global epidemic that has been associated with congenital brain malformations in fetuses and with Guillain-Barre syndrome in adults (GBS). Within the last two years, a major effort has been made to develop murine models to study the mechanism of viral transmission, pathogenesis and the host immune response. Here, we discuss the findings from these models regarding the role that the innate and adaptive immune responses have in controlling ZIKV infection and pathogenesis...
December 20, 2017: Immunology
Sarwat Tahsin Khan, Winston Karges, Curtis L Cooper, Angela M Crawley
Clearance of HCV is dependent on an effective virus-specific CD8+ T-cell response, which is dysfunctional in chronic HCV infection. Dysfunction in bulk or non-HCV specific CD8+ T-cells in HCV infection has also been observed. This may contribute to observed reductions in immunity to other diseases (e.g., cancer, viral co-infections) in HCV-infected individuals. Evidence suggests that the HCV core protein (found in blood as free protein) may contribute to this impairment. To determine if HCV core contributes to the impairment of effector functions and survival potential of CD8+ T-cells, isolated human CD8+ T-cells from healthy donors were pre-incubated with recombinant HCV core protein for 72 hrs and then stimulated in vitro to evaluate proliferation, survival potential and effector functions...
December 20, 2017: Immunology
Hung-Chih Chang, Po-Han Huang, Fu-Sheng Syu, Chia-Hung Hsieh, Sunny Li-Yun Chang, Jean Lu, Hui-Chen Chen
Trafficking and recruitment of immune cells to the site of inflammation with spatial and temporal synchronization is crucial for the development of allergic airway inflammation. Particularly, chemokines are known to be key players in these processes. Previous studies revealed that the CXCL12/CXCR4 axis plays an important role in regulating allergic airway inflammation. However, the role of CXCR7, a recently discovered second receptor for CXCL12, in regulating airway inflammation has not been explored. Initially, CXCR7 was considered as a decoy receptor; however, numerous subsequent studies revealed that engagement of CXCR7 triggered its own signaling or modulated CXCR4-mediated signaling...
December 18, 2017: Immunology
Ariel Podhorzer, Andrés Machicote, Santiago Belen, Leandro Lauferman, Oscar Imventarza, Silvina Montal, Sebastián Marciano, Omar Galdame, Luis G Podesta, Leonardo Fainboim
Deep characterization of the frequencies, phenotypes and functionalities of liver and peripheral blood NK, NKT and T cells from healthy individuals is an essential step to further interpret changes in liver diseases. These data indicate that CCR7, a chemokine essential for cell migration through lymphoid organs, is almost absent in liver NK and T cells. CD56bright NK cells, which represent half of liver NK cells, showed lower expression of the inhibitory molecule NKG2A and an increased frequency of the activatory marker NKp44...
December 16, 2017: Immunology
Nicolas Dubuisson, David Baker, Angray S Kang, Gareth Pryce, Monica Marta, Leo H Visser, Werner E Hofmann, Sharmilee Gnanapavan, Gavin Giovannoni, Klaus Schmierer
Alemtuzumab is a lymphocyte-depleting antibody and one of the most effective treatments for relapsing multiple sclerosis. However, it also causes loss of immune-tolerance leading to secondary autoimmunity and marked anti-drug antibody responses. Whilst these anti-drug responses have been reported to be of no significance, we hypothesised that they will affect the depleting-capacity and treatment-response in some individuals. This was found following analysis of the regulatory submission of the pivotal phase III trials, which was obtained from the European Medicines Agency...
December 16, 2017: Immunology
Danillo Lucas Alves Esposito, Jonathan Ballico de Moraes, Benedito Antonio Lopes da Fonseca
Zika virus (ZIKV), a single-stranded RNA virus of the Flaviviridae family, is an arbovirus (viruses transmitted by arthropods) transmitted to humans and non-human primates through the bites of infected female Aedes sp. mosquitoes. Although first isolated in 1947, only recently it emerged as a global threat, present in several countries resulting in a pandemic scenario. ZIKV infections may result in severe outcomes, such as neurological impairment, and with the intrinsic ability of inducing microcephaly in fetuses of infected pregnant women, the virus has become a major public health problem...
December 15, 2017: Immunology
Temitope W Ademolue, Gordon A Awandare
Immunity to malaria could be categorized broadly as anti-parasite or anti-disease immunity. While most vaccine research efforts have focused on anti-parasite immunity, the evidence from endemic populations suggest that anti-disease immunity is an important component of natural immunity to malaria. The processes that mediate anti-disease immunity have however attracted little to no attention, and most interests have been towards the antibody responses. This review evaluates the evidence for anti-disease immunity in endemic areas and discusses the possible mechanisms responsible for it...
December 6, 2017: Immunology
Nan Jiang, Yan-Fang Xing, Bo Hu, Jian-Xin Tang, Hui-Min Dong, Yu-Mei He, Dan-Yun Ruan, Qing-Jian Ye, Jia-Rong Cai, Xiao-Kun Ma, Jie Chen, Xiu-Rong Cai, Ze-Xiao Lin, Xiang-Yuan Wu, Xing Li
AIM: A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphonuclears myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. METHODS: 127 HCC patients, 10 patients with mild active chronic hepatits B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included...
December 6, 2017: Immunology
Danfeng Guo, Yinghu Chen, Shoujie Wang, Lei Yu, Yingying Shen, Haijun Zhong, Yunshan Yang
Exosomes derived from heat-stressed tumor cells (HS-TEXs), which contain abundant heat shock protein (HSP) 70, strongly induce antitumor immune responses. HSP70-induced interleukin-6 (IL-6) promotes IL-17 expression and causes rejection of established prostate tumors. However, it remains unclear whether HS-TEXs exhibit antitumor effects by converting regulatory T cells (Tregs) into Th17 cells. In this study, we found that compared with TEXs, HS-TEXs were more potent in stimulating secretion of IL-6 from dendritic cells...
December 2, 2017: Immunology
Ilaria Schiavoni, Carolina Scagnolari, Alberto L Horenstein, Pasqualina Leone, Alessandra Pierangeli, Fabio Malavasi, Clara M Ausiello, Giorgio Fedele
Respiratory Syncytial Virus (RSV) is the most common cause of hospitalization due to bronchiolitis in infants. Although the mechanisms behind this association are not completely elucidated, they appear to involve an excessive immune response causing lung pathology. Understanding the host response to RSV infection may help in the identification of targets for therapeutic intervention. We infected in vitro human monocyte-derived dendritic cells (DCs) with RSV and analysed various aspects of the cellular response...
November 27, 2017: Immunology
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