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Lucia Russo, Carey N Lumeng
The expansion of adipose tissue in obesity is accompanied by the accumulation of immune cells that contribute to a state of low-grade, chronic inflammation and dysregulated metabolism. Adipose tissue macrophages (ATMs) represent the most abundant class of leukocytes in adipose tissue (AT) and are involved in the regulation of several regulatory physiological processes such as tissue remodeling and insulin sensitivity. With progressive obesity, ATMs are key mediators of meta-inflammation, insulin resistance, and impairment of adipocyte function...
September 19, 2018: Immunology
María C Ysrraelit, Jorge Correale
Multiple sclerosis (MS) is a chronic inflammatory disease of the Central Nervous System (CNS) affecting young people and leading to demyelination and neurodegeneration. The disease is clearly more common in women in whom incidence has been rising. Gender differences include: earlier disease onset and more frequent relapses in women; and faster progression and worse outcomes in men. Hormone-related physiological conditions in women such as puberty, pregnancy, puerperium and menopause also exert significant influence both on disease prevalence as well as on outcomes...
September 17, 2018: Immunology
Jinghua Wang, Guoping Wu, Brian Manick, Vida Hernandez, Mark Renelt, Christian Erickson, Joanna Guan, Ravinder Singh, Simone Rollins, Alicia Solorz, Ming Bi, Jun Li, David Grabowski, Janette Dirkx, Camrin Tracy, Thomas Stuart, Chad Ellinghuysen, Daniel Desmond, Craig Foster, Vassilios Kalabokis
B7 family members and their receptors play a central role in the regulation of T cell responses through T cell costimulation and coinhibition pathways that constitute very attractive targets for the development of immunotherapeutic drugs. In this study, we report that VSIG-3/IGSF11 is a ligand of B7 family member VISTA/PD-1H and inhibits human T cell functions through a novel VSIG-3/VISTA pathway. An extensive functional ELISA binding screening assay reveals that VSIG-3 does bind to the new B7 family member VISTA but does not interact with other known members of the B7 family...
September 16, 2018: Immunology
Ticiana Della Justina Farias, Danillo G Augusto, Rodrigo Coutinho de Almeida, Danielle Malheiros, Maria Luiza Petzl-Erler
Pemphigus foliaceus (PF) is a blistering autoimmune skin disease rare in most of the world but endemic in certain regions of Brazil. PF is characterized by the detachment of epidermal cells and the presence of autoantibodies against desmoglein 1. In previous studies, we have shown that genetic polymorphisms and variable expression levels of certain leukocyte receptor complex (LRC) genes were associated with PF. However, the role of the LRC on PF susceptibility remained to be investigated. Here, we analyzed 527 tag single nucleotide polymorphisms (SNP) distributed within the 1...
September 14, 2018: Immunology
O Rossi, C Coward, Y S Goh, J W C Claassens, C A MacLennan, Sjef J Verbeek, P Mastroeni
Vaccines can serve as essential tools to prevent bacterial diseases via the induction of long-lasting IgG responses. The efficacy of such vaccines depends on the effector mechanisms triggered by IgG. The complement system and Fc-gamma Receptors (FcγR) can potentially play a crucial role in IgG-mediated immunity against bacterial diseases. However, their relative importance in vivo is unclear and has been the object of controversy and debate. In this brief study, we have used gene-targeted mice lacking either FcγRI,II,II and IV or the C3 complement component as well as a novel mouse strain lacking both C3 and FcγRs to conclusively show the essential role of complement in antibody-mediated host resistance to Salmonella enterica systemic infection...
September 4, 2018: Immunology
Jiajing Liu, Yifan Li, Zhou Lu, Jie Gu, Yun Liang, Enyu Huang, Zhiming Wang, Hushan Zhang, Luman Wang, Dan Zhang, Hongxiu Yu, Ronghua Liu, Yiwei Chu
B lymphocytes, known as antibody producers, mediate tumor-cell destruction in the manner of antibody-dependent cell-mediated cytotoxicity; however, their anti-tumor function seems to be weakened during tumorigenesis; while, the mechanisms underlying remained unclear. In this study, we found that IgG mediated anti-tumor effect, but IgG-producing B cells decreased in various tumors. Considering the mechanism underlying, glycometabolism was noteworthy. We found that tumor-infiltrating B cells were glucose-starved and accompanied by a deceleration of glycometabolism...
September 1, 2018: Immunology
Xiaorong Zhou, Weiwei Xian, Jie Zhang, Yiqing Zhu, Xiaoyi Shao, Yu Han, Yue Qi, Xiaoling Ding, Xiaoying Wang
The rearrangement and expression of immunoglobulin genes are regulated by enhancers and their binding transcriptional factors that activate or suppress the activities of the enhancers. The immunoglobulin κ (Igκ) gene locus has three important enhancers: the intrinsic enhancer (Ei), 3' enhancer (E3'), and distal enhancer (Ed). Ei and E3' are both required for Igκ gene rearrangement during early stages of B-cell development, whereas optimal expression of the rearranged Igκ gene relies on both E3' and Ed. The transcription factor YY1 affects the expression of many genes involved in B-cell development, probably by mediating interactions between their enhancers and promoters...
August 29, 2018: Immunology
Naresh Kumar Meena, Shakti Prasad Pattanayak, Yael Ben-Nun, Sandrine Benhamron, Saran Kumar, Emmanuelle Merquiol, Nadine Hövelmeyer, Galia Blum, Boaz Tirosh
mTORC1 is a key regulator of cell metabolism and lymphocyte proliferation. mTORC1 is inhibited by the tuberous sclerosis complex (TSC), a heterodimer of TSC1 and TSC2. Deletion of either genes results in robust activation of mTORC1. Mature B cells reside in the spleen at two major anatomical locations, the marginal zone (MZ) and follicles. MZ constitute the first line of humoral response against blood-borne pathogens and undergoes atrophy in chronic inflammation. In previous work we showed that mice deleted for TSC1 in their B cells (TSC1BKO ) have almost no MZ B cells, while follicular B cells are minimally affected...
August 24, 2018: Immunology
Shin-Ichi Inoue, Mamoru Niikura, Hiroko Asahi, Yasushi Kawakami, Fumie Kobayashi
It is unclear whether γδ T cells are involved in humoral immunity against Plasmodium infection. Here, we show that B cell-immunodeficient mice and γδ T cell-deficient mice were incapable of protecting against Plasmodium berghei XAT parasites. γδ T cell-deficient mice developed reduced levels of antigen-specific antibodies during the late phase of infection. The numbers of follicular helper T cells and germinal centre B cells in γδ T cell-deficient mice were lower than in wild-type mice during the late phase of infection...
August 24, 2018: Immunology
Santosh Kumar, Shweta Jain
Formation of supramolecular assemblies appears to be a general mechanism in immune signaling pathways. These supramolecular assemblies appear to form through a nucleated polymerization mechanism. This review examines selected immune signaling pathways that involve supramolecular assemblies, describes the concepts of protein polymerization, and discusses how those concepts of protein polymerization implicate new elegant ways for signal amplification, setting threshold, and noise reduction in these pathways. This article is protected by copyright...
August 24, 2018: Immunology
Aoi Akitsu, Yoichiro Iwakura
Interleukin-17 (IL-17) is a pro-inflammatory cytokine and is involved in the development of many diseases. Recent studies have revealed that IL-17-producing γδ T cells (γδ17 cells) in addition to IL-17-producing CD4+ T cells [T helper type 17 (Th17) cells] are often the main producers of IL-17 in mouse models of inflammatory diseases. γδ T cells are functionally committed during intra-thymic differentiation. γδ thymocytes capable of producing IL-17, which express the transcription factor retinoic-acid-receptor-related orphan receptor γt and the signature cytokine receptor IL-23R, leave the thymus, and produce IL-17 rapidly by the stimulation with IL-1β and IL-23 in the periphery...
August 22, 2018: Immunology
Cuilian Liu, Haoran Yang, Weiyun Shi, Ting Wang, Qingguo Ruan
Th17 cells and regulatory T (Treg) cells are two distinct T cell subsets which have opposite effects on immune functions. While Th17 cells are a key effector in the immune response and play critical roles in the development of autoimmunity and inflammation, Treg cells orchestrate the overall immune response and maintain peripheral immune tolerance by regulating the activity of the effector T cells. However, the developmental pathways for Th17 and Treg cells are reciprocally interconnected and there is a significant amount of plasticity between them...
August 22, 2018: Immunology
Cinthia Nóbrega de Sousa Dias, Bruna Macêdo Gois, Viviane Silva Lima, Isabel Cristina Guerra-Gomes, Josélio Maria Galvão Araújo, Juliana de Assis Silva Gomes, Demétrius Antônio Machado Araújo, Isac Almeida Medeiros, Fátima de Lourdes Assunção Araújo de Azevedo, Robson Cavalcanti Veras, Daniele Idalino Janebro, Ian Porto Gurgel do Amaral, Tatjana Souza Lima Keesen
There is a need for more detailed elucidation of T-cell immunity in chikungunya infection. CD8 T cells are one of main actors against viruses. Here, we analysed CD8+ T lymphocytes from patients in the acute and chronic phases of chikungunya disease (CHIKD). Our results demonstrate that CD8+ T cells expressed higher ex vivo granzyme B, perforin and CD107A expression in patients in the acute phase of CHIKD compared with healthy individuals and higher ex vivo expression of CD69, interleukin-17A, interleukin-10 and CD95 ligand, and co-expression of CD95/CD95 ligand...
August 12, 2018: Immunology
Rafael E Marques, Anne-Gaëlle Besnard, Isabelle Maillet, Caio T Fagundes, Danielle G Souza, Bernhard Ryffel, Mauro M Teixeira, Foo Y Liew, Rodrigo Guabiraba
The excessive inflammation often present in patients with severe dengue infection is considered both a hallmark of disease and a target for potential treatments. Interleukin-33 (IL-33) is a pleiotropic cytokine with pro-inflammatory effects whose role in dengue has not been fully elucidated. We demonstrate that IL-33 plays a disease-exacerbating role during experimental dengue infection in immunocompetent mice. Mice infected with dengue virus serotype 2 (DENV2) produced high levels of IL-33. DENV2-infected mice treated with recombinant IL-33 developed markedly more severe disease compared with untreated mice as assessed by mortality, granulocytosis, liver damage and pro-inflammatory cytokine production...
August 11, 2018: Immunology
Xiao-Hua Luo, Qingda Meng, Martin Rao, Zhenjiang Liu, Georgia Paraschoudi, Ernest Dodoo, Markus Maeurer
Human cytomegalovirus (CMV) is a ubiquitous, persistent beta herpesvirus. CMV infection contributes to the accumulation of functional antigen (Ag)-specific CD8+ T-cell pools with an effector-memory phenotype and enrichment of these immune cells in peripheral organs. We review here this "memory T-cell inflation" phenomenon and associated factors including age and sex. 'Collateral damage' due to CMV-directed immune reactivity may occur in later stages of life - arising from CMV-specific immune responses that were beneficial in earlier life...
August 11, 2018: Immunology
Pablo Palazon-Riquelme, Gloria Lopez-Castejon
As a result of its strategic location, the epithelium is constantly exposed to a wide variety of pathogen and danger signals. Traditionally, the epithelium has been perceived as a defensive but passive barrier; however, it has now become evident that the epithelium senses and actively responds to these signals in order to maintain barrier homeostasis and contributes to the inflammatory response. One way it does this is by producing pro-inflammatory cytokines including interleukin-1β (IL-1β) and IL-18. These two cytokines are synthesized as inactive precursors, the maturation of which is mediated by pro-inflammatory caspases after the activation and assembly of macromolecular complexes called inflammasomes...
August 11, 2018: Immunology
Lucas Souza Ferreira, Deivys Leandro Portuondo, Marisa Campos Polesi, Iracilda Zeppone Carlos
Natural killer (NK) cells are one of the first cell types to enter inflammation sites and have been historically known as key effector cells against tumours and viruses; now, accumulating evidence shows that NK cells are also capable of direct in vitro activity and play a protective role against clinically important fungi in vivo. However, our understanding of NK cell development, maturation and activation in the setting of fungal infections is preliminary at best. Sporotrichosis is an emerging worldwide-distributed subcutaneous mycosis endemic in many countries, affecting humans and other animals and caused by various related thermodimorphic Sporothrix species, whose prototypical member is Sporothrix schenckii...
July 20, 2018: Immunology
Mitra Bhattacharyya, James B Whitney, Michael Seaman, Dan H Barouch, Pablo Penaloza-MacMaster
Antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) infection represents a major breakthrough in the treatment of HIV/acquired immune-deficiency syndrome. However, it remains unclear how ART influences virus-specific immune responses and understanding this is important for developing novel cure and eradication interventions for HIV-1. In the present study, we evaluate how ART impacts T-cell and antibody responses in simian immunodeficiency virus (SIV) -infected rhesus macaques...
July 17, 2018: Immunology
Sandeep K Dhanda, Kerrie Vaughan, Veronique Schulten, Alba Grifoni, Daniela Weiskopf, John Sidney, Bjoern Peters, Alessandro Sette
Epitopes identified in large-scale screens of overlapping peptides often share significant levels of sequence identity, complicating the analysis of epitope-related data. Clustering algorithms are often used to facilitate these analyses, but available methods are generally insufficient in their capacity to define biologically meaningful epitope clusters in the context of the immune response. To fulfil this need we developed an algorithm that generates epitope clusters based on representative or consensus sequences...
July 17, 2018: Immunology
Min Yang, Katrin Klocke, Clara Marquina Hernandez, Bingze Xu, Inger Gjertsson, Kajsa Wing, Rikard Holmdahl
CD4+  Foxp3+ regulatory T (Treg) cells can control both cellular and humoral immune responses; however, when and how Treg cells play a predominant role in regulating autoimmune disease remains elusive. To deplete Treg cells in vivo at given time-points, we used a mouse strain, susceptible to glucose-6-phosphate isomerase peptide-induced arthritis (GIA), in which the deletion of Treg cells can be controlled by diphtheria toxin treatment. By depleting Treg cells in the GIA mouse model, we found that a temporary lack of Treg cells at both priming and onset exaggerated disease development...
July 10, 2018: Immunology
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