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Immunology

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https://www.readbyqxmd.com/read/28921535/genome-wide-host-rna-signatures-of-infectious-diseases-discovery-and-clinical-translation
#1
REVIEW
Harriet D Gliddon, Jethro A Herberg, Michael Levin, Myrsini Kaforou
The use of whole blood gene expression to derive diagnostic biomarkers capable of distinguishing between phenotypically similar diseases holds great promise but remains a challenge. Differential gene expression analysis is used to identify the key genes that undergo changes in expression relative to healthy individuals, as well as to patients with other diseases. These key genes can act as diagnostic, prognostic and predictive markers of disease. Gene expression 'signatures' in the blood hold potential to be used for the diagnosis of infectious diseases, where current diagnostics are unreliable, ineffective or of limited potential...
September 16, 2017: Immunology
https://www.readbyqxmd.com/read/28921511/bone-marrow-ilc2s-a-local-source-of-il-5-in-il-33-driven-eosinophilia
#2
Kristina Johansson, Carina Malmhäll, Patricia Ramos-Ramírez, Madeleine Rådinger
T helper type 2 (TH 2) cells, type 2 innate lymphoid cells (ILC2s) and eosinophil progenitors have previously been described to produce IL-5 in the airways upon allergen provocation or by direct administration of IL-33. Eosinophilic airway inflammation is known to be associated with IL-5-dependent eosinophil development in the bone marrow, however, the source of IL-5 remains unclear. TH cells, ILC2s and CD34(+) progenitors have been proposed to be involved in this process, therefore, we investigated whether these cells are taking part in eosinophilopoiesis by producing IL-5 locally in the bone marrow in IL-33-driven inflammation...
September 16, 2017: Immunology
https://www.readbyqxmd.com/read/28898398/integrating-high-throughput-screening-and-sequencing-for-monoclonal-antibody-discovery-and-engineering
#3
REVIEW
Cristina Parola, Daniel Neumeier, Sai T Reddy
Monoclonal antibody discovery and engineering is a field that has traditionally been dominated by high-throughput screening platforms (e.g., hybridomas and surface display). In recent years the emergence of high-throughput sequencing has made it possible to obtain large-scale information on antibody repertoire diversity. Additionally, it has now become more routine to perform high-throughput sequencing on antibody repertoires to also directly discover antibodies. In this review, we provide an overview of the progress in this field to date and show how high-throughput screening and sequencing are converging to deliver powerful new workflows for monoclonal antibody discovery and engineering...
September 12, 2017: Immunology
https://www.readbyqxmd.com/read/28898397/genome-wide-dna-methylation-analysis-of-senescence-in-repetitively-infected-memory-ctls-dna-methylation-analysis-of-repetitively-infected-memory-ctls
#4
Jumpei Shosaku
The immune system including antigen-specific CD8 T cells, which are cytotoxic T lymphocytes (CTLs), can acquire the potential of more effective elimination of the pathogen for reinfection. Since memory CTLs could exert protective immunity after the next response, we aimed to elucidate the substantial change of repetitively infected memory CTLs. Currently, DNA methylation status in repetitively infected memory CTLs is still unknown. Therefore, we performed next generation sequencing (NGS) to evaluate methylation status and transcriptional regulation of naive, primary and secondary memory CD8 T cells on the basis of transcription start sites (TSS)...
September 12, 2017: Immunology
https://www.readbyqxmd.com/read/28898395/endogenous-lipid-antigens-for-invariant-natural-killer-t-cells-hold-the-reins-in-adipose-tissue-homeostasis
#5
REVIEW
Robert J van Eijkeren, Olga Krabbe, Marianne Boes, Henk S Schipper, Eric Kalkhoven
The global obesity epidemic and its associated co-morbidities, including type 2 diabetes, cardiovascular disease and certain types of cancers, have drawn attention to the pivotal role of adipocytes in health and disease. Besides their 'classical' function in energy storage and release, adipocytes interact with adipose-tissue resident immune cells, among which lipid-responsive invariant Natural Killer T (iNKT) cells. iNKT cells are activated by lipid antigens presented by antigen-presenting cells (APC) as CD1d/lipid complexes...
September 12, 2017: Immunology
https://www.readbyqxmd.com/read/28892130/fgl2-deteriorates-cardiac-function-in-experimental-autoimmune-myocarditis-rats-through-regulation-of-pd-1-and-inflammatory-cytokines
#6
Zhenzhong Zheng, Yinghui Yu, Ratnakar Potla, Yujing Wu, Hao Wu
PD-1 plays an important role in protecting against inflammation and myocyte damage in T cell mediated myocarditis. To understand whether FGL2 can affect the role of PD-1/PD-L1 pathway in experimental autoimmune myocarditis (EAM),we investigated the cardiac function in EAM rats overexpressing FGL2. Overexpression of FGL2 significantly decreased PD-1 and deteriorated cardiac function in autoimmune myocarditis rats. Histopathology revealed increased inflammatory cell infiltrate in EAM-FGL2 rats compared to the control groups (EAM, EAM-GFP, and NC)...
September 11, 2017: Immunology
https://www.readbyqxmd.com/read/28892129/invariant-natural-killer-t-cell-development-and-function-with-loss-of-microrna-155
#7
Adolfo B Frias, Heather M Buechel, Arpan Neupane, Louise M D'Cruz
Invariant Natural Killer T (iNKT) cells are adaptive T cells with innate-like characteristics including rapid cytokine production and proliferative response to stimulation. Development of these cells in the thymus is dependent on expression of the microRNA (miRNA) processing enzyme Dicer indicating iNKT cells likely have distinct miRNA requirements for gene regulation during development. The miRNA, miR-155, has previously been shown to have numerous roles in T cells, including regulation of proliferation and differentiation and positive modulation of IFN-γ expression...
September 11, 2017: Immunology
https://www.readbyqxmd.com/read/28888033/modulation-of-%C3%AE-%C3%AE-t-cell-activation-by-neutrophil-elastase
#8
Nadia Yasmín Towstyka, Carolina Maiumi Shiromizu, Irene Keitelman, Florencia Sabbione, Gabriela Verónica Salamone, Jorge Raúl Geffner, Analía Silvina Trevani, Carolina Cristina Jancic
γδ T cells are non-conventional, innate-like T cells, characterized by a restricted TCR repertoire. They participate in protective immunity response against extracellular and intracellular pathogens, tumor surveillance, modulation of innate and adaptive immune responses, tissue healing, epithelial cell maintenance, and regulation of physiological organ function. In this study, we investigated the role of neutrophils during the activation of human blood γδ T cells through CD3 molecules. We found that the up-regulation of CD69 expression, and the production of IFN-γ and TNF-α induced by anti-CD3 antibodies were potentiated by neutrophils...
September 9, 2017: Immunology
https://www.readbyqxmd.com/read/28881482/altered-expression-of-antigen-specific-memory-and-regulatory-t-cell-subsets-differentiate-latent-and-active-tuberculosis
#9
Balaji Pathakumari, Santhi Devasundaram, Alamelu Raja
Though one-third of the world population is infected with M. tuberculosis, only 5-10% of the infected individuals will develop active TB disease and rest will remain infected with no symptoms known as latent TB infection (LTBI). Identifying biomarkers that differentiate latent and active TB disease enables effective TB control, since early detection, treatment of active TB and preventive treatment of LTBI individuals are crucial steps involved in TB control. Here, we have evaluated the frequency of antigen specific memory and regulatory T cells (Tregs) in 15 healthy household contacts (HHC) and 15 pulmonary TB patients (PTB) to identify biomarkers for differential diagnosis of LTBI and active TB...
September 7, 2017: Immunology
https://www.readbyqxmd.com/read/28881401/generation-of-t-follicular-helper-cells-in-vitro-requirement-for-bcr-cross-linking-and-cognate-b-and-t-cell-interaction
#10
Anne Kolenbrander, Bastian Grewe, David Nemazee, Klaus Überla, Vladimir Temchura
The minimal requirements for in vitro modeling of the natural CD4(+) T-cell differentiation into T follicular helper (TFH) cells are still under investigation. We co-cultured wild type and TCR-transgenic CD4(+) T-cells from naïve mice with dendritic cells and BCR-transgenic B-cells in the presence of HIV-derived virus-like particles containing matched B- and T-cell epitopes. This co-culturing induced co-expression of TFH-master regulator transcription factor BCL-6 and CXCR5 in up to 10% of the wild type and up to 40% of the TCR-transgenic CD4(+) T-cells...
September 7, 2017: Immunology
https://www.readbyqxmd.com/read/28880992/innate-lymphoid-cells-at-the-interface-between-obesity-and-asthma
#11
REVIEW
Laetitia Everaere, Saliha Ait Yahia, Mélodie Bouté, Camille Audousset, Cécile Chenivesse, Anne Tsicopoulos
Obesity and asthma prevalence has dramatically and concomitantly increased over the last 25 years, and many epidemiological studies have highlighted obesity as an important risk factor for asthma. Although many studies have been performed, the underlying mechanisms remain poorly understood. Innate mechanisms have been involved in both diseases in particular through the recently described innate lymphoid cells (ILCs). ILCs are subdivided in three groups that are defined by their cytokine production and by their master transcription factor expression, in sharp correlation with their T helper counterparts...
September 7, 2017: Immunology
https://www.readbyqxmd.com/read/28872671/wnt7a-induces-a-unique-phenotype-of-monocyte-derived-macrophages-with-lower-phagocytic-capacity-and-differential-expression-of-pro-and-anti-inflammatory-cytokines
#12
Jennillee Wallace, Victoria Lutgen, Sreedevi Avasarala, Brad St Croix, Robert A Winn, Lena Al-Harthi
The variation of macrophage functions suggests the involvement of multiple signaling pathways in fine tuning their differentiation. Macrophages that originate from monocytes in the blood migrate to tissue in response to homeostatic or "danger" signals and undergo substantial morphological and functional modifications to meet the needs of the dominant signals in the microenvironment. Wnts are secreted glycoproteins that play a significant role in organ and cell differentiation, yet their impact on monocyte differentiation is not clear...
September 5, 2017: Immunology
https://www.readbyqxmd.com/read/28871661/update-on-aire-and-thymic-negative-selection
#13
REVIEW
Geraldo Aleixo Passos, Cesar A Speck-Hernandez, Amanda Freire Assis, Daniella A Mendes-da-Cruz
Twenty years ago, the autoimmune regulator (Aire) gene was associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), cloned and sequenced. Its importance goes beyond its link with human autoimmune disease. Aire identification opened new perspectives to better understand the molecular basis of central tolerance and self-non-self-distinction, the main properties of the immune system. During these two last decades, a growing number of immunologists and molecular geneticists have made important discoveries about the function of Aire, which is essentially a pleiotropic gene...
September 4, 2017: Immunology
https://www.readbyqxmd.com/read/28869761/novel-viral-vectors-in-infectious-diseases
#14
REVIEW
Ian R Humphreys, Sarah Sebastian
Since the development of Vaccinia virus as a vaccine vector in 1984, the utility of numerous viruses in vaccination strategies has been explored. In recent years, key improvements to existing vectors such as those based on adenovirus have led to significant improvements in immunogenicity and efficacy. Furthermore, exciting new vectors that exploit viruses such as cytomegalovirus (CMV) and vesicular stomatitis virus (VSV) have emerged. Herein, we summarize these recent developments in viral vector technologies, focusing on novel vectors based on CMV, VSV, measles and modified adenovirus...
September 4, 2017: Immunology
https://www.readbyqxmd.com/read/28833085/development-of-a-strategy-and-computational-application-to-select-candidate-protein-analogs-with-reduced-hla-binding-and-immunogenicity
#15
Sandeep Kumar Dhanda, Alba Grifoni, John Pham, Kerrie Vaughan, John Sidney, Bjoern Peters, Alessandro Sette
Unwanted immune responses against protein therapeutics can reduce efficacy or lead to adverse reactions. T cell responses are key in the development of such responses, and are directed against immunodominant regions within the protein sequence, often associated with binding to several allelic variants of HLA class II molecules (promiscuous binders). Herein, we report a novel computational strategy to predict 'deimmunized' peptides, based on previous studies of erythropoietin (EPO) protein immunogenicity. This algorithm (or method) first predicts promiscuous binding regions within the target protein sequence and then identifies residue substitutions predicted to reduce HLA binding...
August 22, 2017: Immunology
https://www.readbyqxmd.com/read/28833081/transcriptional-repressor-blimp1-regulates-follicular-regulatory-t-cells-homeostasis-and-function
#16
Guang Yang, Xiaosu Yang, Junmei Zhang, Guancheng Li, Dandan Zheng, Anjiao Peng, Jue Hu, Liqun Xu, Baifeng Yang, Huan Yang, Wenbin Zhou, Erdem Tuzun, Jing Li
The B lymphocyte-induced maturation protein 1(Blimp1) regulates T cell homeostasis and function. Loss of Blimp1 could double the proportion of TFR cells. However, the effects that Blimp1 may have on the function of TFR cells remain unknown. Here we document the function for Blimp1 in TFR cells in vitro and in vivo. Data presented in this study demonstrated that TFR cells indirectly inhibit the activation and differentiation of B cells by negatively regulating TFH cells, thus lowering the secretion of antibody...
August 20, 2017: Immunology
https://www.readbyqxmd.com/read/28815581/th1-polarizing-%C3%AE-%C3%AE-t-cells-and-scavenger-receptors-contribute-to-the-pathogenesis-of-pemphigus-vulgaris
#17
Dayasagar Das, Vivek Anand, Sujay Khandpur, V K Sharma, Alpana Sharma
Gamma delta T cells (γδ T cells) and Scavenger receptors are key innate immune machinery playing significant role in regulating immune homeostasis at epithelial surface. The roles of these immune components are not yet characterized for the autoimmune skin disorder Pemphigus Vulgaris (PV). Phenotyping and frequency of γδ T cells estimated by Flowcytometry has shown increased frequency of γδ T cells (6.7% vs. 4.4%) producing IFN-γ (35.2% vs. 26.68%), in circulation of patients compared to controls. Dual cytokine (IFN-γ & IL-4) secreting γδ T cells indicate plasticity of these cells...
August 16, 2017: Immunology
https://www.readbyqxmd.com/read/28804903/targeting-of-tolerogenic-dendritic-cells-towards-heat-shock-proteins-a-novel-therapeutic-strategy-for-autoimmune-diseases
#18
REVIEW
Manon A A Jansen, Rachel Spiering, Femke Broere, Jacob M van Laar, John D Isaacs, Willem van Eden, Catharien M U Hilkens
Tolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. The rationale of using tolDCs is that they can specifically target the pathogenic T cell response, while leaving other, protective T cell responses intact. Several ways of generating therapeutic tolDCs have been described, but whether these tolDCs should be loaded with autoantigen(s), and if so, with which autoantigen(s), remains unclear. Autoimmune diseases, such as rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen...
August 14, 2017: Immunology
https://www.readbyqxmd.com/read/28799262/the-regulation-of-regulation-il-10-increases-cd4-cd25-regulatory-t-cells-but-impairs-their-immunosuppressive-activity-in-murine-models-with-schistosomiasis-japonica-or-asthma
#19
Lei He, Sha Zhou, Qianqian Qi, Ying Chi, Jifeng Zhu, Zhipeng Xu, Xuefeng Wang, Jason Hoellwarth, Feng Liu, Xiaojun Chen, Chuan Su
CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) play an important role in maintaining immune homeostasis. Interleukin 10 (IL-10), a cytokine with anti-inflammatory capacities, also has a critical role in controlling immune responses. In addition, it is well known that production of IL-10 is one of suppression mechanisms by Tregs. However, the action of IL-10 on Tregs themselves remains insufficiently understood. In this study, by using a Schistosoma japonicum (S. japonicum)-infected murine model, we show that the elevated IL-10 contributed to Treg induction but impaired their immunosuppressive function...
August 11, 2017: Immunology
https://www.readbyqxmd.com/read/28799242/negative-regulation-of-nlrp3-inflammasome-activation-by-tim-3-protects-against-peritonitis
#20
Wei Wang, Qingzhu Shi, Shuaijie Dou, Ge Li, Xinhui Shi, Xingwei Jiang, Zhiding Wang, Dandan Yu, Guojiang Chen, Wang Ren Xi, He Xiao, Chunmei Hou, Jiannan Feng, Beifen Shen, Yuanfang Ma, Gencheng Han
The NLRP3 inflammasome plays roles in host defense against invading pathogens and in the development of autoimmune damage. Strict regulation of these responses is important to avoid detrimental effects. Here, we demonstrate that Tim-3, an immune checkpoint inhibitor, inhibits NLRP3 inflammasome activation by damping basal and LPS-induced NF-κB-mediated upregulation of NLRP3 and IL-1β during the priming step and basal and ATP/LPS-induced ATP production, K(+) efflux, and ROS production during the activation step...
August 11, 2017: Immunology
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