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Ruoyu Wu, Bi Chen, Xiang Jia, Yu Qiu, Mengyu Liu, Chengsheng Huang, Jie Feng, Qingkai Wu
OBJECTIVE: This study focuses on investigating the role of interleukin-1 beta (IL-1β) in functional regeneration following nerve injury in mice. METHODS: A microarray-based mRNA profiling study was used to analyze the expression level of IL-1β in peripheral nerve regeneration. QRT-PCR and western blot were applied to assess the IL-1β expressions of C57BL/6J-crush and C57BL/6J-crush+IL-1β mice at different post-injury time points after the standard sciatic nerve crush injury...
November 12, 2018: Immunology
Chu-Lun Lin, Huei-Mei Huang, Chia-Ling Hsieh, Chia-Kwung Fan, Yueh-Lun Lee
Dendritic cells (DCs) are professional antigen-presenting cells that play a key role in directing T cell responses. Regulatory T (Treg) cells possess an immunosuppressive ability to inhibit effector T cell responses, and Notch ligand Jagged1 (Jag1) was implicated in Treg cell differentiation. In this study, we evaluated whether bone marrow-derived DCs (BMDCs) genetically engineered to express Jag1 (Jag1-DCs) would affect the maturation and function of DCs in vitro, and further investigated the immunoregulatory ability of Jag1-DCs to manipulate T helper type 2 (Th2)-mediated allergic asthma in mice...
November 12, 2018: Immunology
Anna Mestre-Ferrer, Erika Scholz, Jepi Humet-Alsius, Iñaki Alvarez
MHC genes are highly polymorphic, what makes each MHC molecule different regarding the peptide repertoire they can bind and present to T lymphocytes. The increasing importance of immunopeptidomics and its use in personalized medicine in different fields as oncology or autoimmunity demands the correct analysis of the peptide repertoires bound to HLA-I and -II molecules. Purification of the peptide pool by affinity chromatography and individual peptide sequencing using mass spectrometry techniques is the standard protocol to define the binding motifs of the different MHC-I and MHC-II molecules...
November 8, 2018: Immunology
Bhawana Singh, Michaela Fakiola, Medhavi Sudarshan, Joyce Oommen, Siddarth Sankar Singh, Shyam Sundar, Jenefer M Blackwell
Genetic variation at HLA-DRB1 is a risk factor for visceral leishmaniasis (VL) caused by Leishmania donovani. The single nucleotide polymorphism rs9271252 upstream of the DRB1 gene provides a perfect tag for protective versus risk HLA-DRB1 4-digit alleles. In addition to the traditional role of the membrane-distal region of HLA class II molecules in antigen presentation and CD4 T cell activation, the membrane-proximal region mediates "non-traditional" multi-functional activation, differentiation, or death signals, including in DR-expressing T cells...
November 7, 2018: Immunology
Christopher G Bazewicz, Saketh S Dinavahi, Todd D Schell, Gavin P Robertson
The role of aldehyde dehydrogenase (ALDH) in carcinogenesis and resistance to cancer therapies is well known. Mounting evidence also suggests a potentially important role for ALDH in the induction and function of regulatory T cells (Tregs ). Tregs are important cells of the immune system involved in promoting immune tolerance and preventing aberrant immune responses to beneficial or non-harmful antigens. However, Tregs also impair tumor immunity, leading to the progression of various carcinomas. ALDH expression and the subsequent production of retinoic acid by numerous cells including dendritic cells, macrophages, eosinophils and epithelial cells seems important in Treg induction and function in multiple organ systems...
November 2, 2018: Immunology
Dennis Montoya, Manali Mehta, Benjamin G Ferguson, Rosane M B Teles, Stephan R Kruzik, Daniel Cruz, Matteo Pellegrini, Robert L Modlin
Macrophage (MΦ) polarization is triggered during the innate immune response to defend against microbial pathogens, but can also contribute to disease pathogenesis. In a previous study, we found that IL-15 derived M1 MΦ have enhanced antimicrobial activity, whereas IL-10 derived M2 MΦ were highly phagocytic but lacked antimicrobial activity. Given that the ability to modulate MΦ polarization from M2 MΦ to M1 MΦ may promote a more effective immune response to infection, we investigated the plasticity of these MΦ programs...
October 24, 2018: Immunology
Diana M Elizondo, Temesgen E Andargie, Naomi L Haddock, Thomas A Boddie, Michael W Lipscomb
Phagocytosis, macropinocytosis and antigen presentation by dendritic cells (DC) requires reorganization of the actin cytoskeleton. Drebrin (Dbn1) is an actin binding and stabilizing protein with roles in endocytosis, formation of dendrite spines in neurons and coordinating cell-cell synapses in immune cells. However, its role in DC phagocytosis and antigen presentation is unknown. These studies now report that silencing of Dbn1 in DC resulted in restrained cell surface display of receptors, most notably MHC class I and II and costimulatory molecules...
October 14, 2018: Immunology
René H M Raeven, Elly van Riet, Hugo D Meiring, Bernard Metz, Gideon F A Kersten
Systems vaccinology has proven a fascinating development in the last decade. Where traditionally vaccine development has been dominated by trial and error, systems vaccinology is a tool that provides novel and comprehensive understanding if properly used. Datasets retrieved from systems-based studies endorses rational design and effective development of safe and efficacious vaccines. In this review we first describe different omics-techniques that form the pillars of systems vaccinology. In the second part, the application of systems vaccinology in the different stages of vaccine development is described...
October 14, 2018: Immunology
Juan S Naranjo-Gómez, Andrés Castillo, Mauricio Rojas, Bertha N Restrepo, Francisco J Diaz, Paula A Velilla, Diana Castaño
Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that monocyte subsets (classical, intermediate and non-classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non-classical monocytes in patients than in controls...
October 13, 2018: Immunology
Johannes Breuning, Brian Philip, Marion H Brown
T cells expressing chimeric antigen receptors (CARs) are a promising new cancer immunotherapy that has now reached the clinic. CARs are synthetic receptors that redirect T cells towards a tumour-associated antigen and activate them through various fused signalling regions, for example derived from CD3ζ, 4-1BB or CD28. Analysis of the optimal combination of CAR components including signalling domains is not yet comprehensive and may vary with the particular application. The C-terminus of the T-cell surface receptor CD6 is critical for its co-stimulatory effects and signals through two phospho-tyrosine motifs that bind to the intracellular adaptor proteins GADS and SLP-76...
October 9, 2018: Immunology
Jinlei He, Fan Huang, Jianhui Zhang, Han Chen, Qiwei Chen, Junrong Zhang, Jiao Li, Zhiwan Zheng, Dali Chen, Jianping Chen
Visceral leishmaniasis is a tropical and neglected disease with an estimated 200 000-400 000 cases and 60 000 deaths worldwide each year. Currently, no clinically valid vaccine is available for this disease. In this study, we formulated DNA and protein vaccines encoding HLA-A2, HLA-A24 and HLA-DR1 restricted epitopes of CaNA2 against visceral leishmaniasis. We predicted the secondary and tertiary structures, surface properties, subcellular localization, potential binding sites and HLA-A2, HLA-A24 and HLA-DR1 restricted epitopes of CaNA2...
October 4, 2018: Immunology
Naoki Iwanaga, Jay K Kolls
Interleukin-17 (IL-17)-producing cells play a critical role in mucosal immunity including the respiratory tract. This review will highlight recent advances in our understanding of these cells in mucosal immunity in the lung as well as their potential pathogenic roles in respiratory diseases. The IL-17-producing cells include γδ T cells, natural killer cells, group 3 innate lymphoid cells, and T helper type 17 (Th17) cells. There have been recent advances in our understanding of these cell populations in the lung as well as emerging data on how these cells are regulated in the lung...
September 27, 2018: Immunology
Sara Costa, Dalila Bevilacqua, Marco A Cassatella, Patrizia Scapini
An increasing body of literature supports a role for neutrophils as players in the orchestration of adaptive immunity. During acute and chronic inflammatory conditions, neutrophils rapidly migrate not only to sites of inflammation, but also to draining lymph nodes and spleen, where they engage bidirectional interactions with B- and T-lymphocyte subsets. Accordingly, a relevant role of neutrophils in modulating B-cell responses under homeostatic conditions has recently emerged. Moreover, specialized immunoregulatory properties towards B or T cells acquired by distinct neutrophil populations, originating under pathological conditions, have been consistently described...
September 27, 2018: Immunology
Lucia Russo, Carey N Lumeng
The expansion of adipose tissue (AT) 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 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 co-stimulation and co-inhibition pathways that constitute 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 binds 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 leucocyte receptor complex (LRC) genes were associated with PF. However, the role of the LRC on PF susceptibility remained to be investigated. Here, we analysed 527 tag single nucleotide polymorphisms (SNPs) distributed within the 1·5 Mb LRC...
September 14, 2018: Immunology
Omar Rossi, Chris Coward, Yun Shan Goh, Jill W C Claassens, Calman A MacLennan, Sjef J Verbeek, Pietro 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 (FcγRs) 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 underlying mechanisms remain unclear. In this study, we found that IgG mediated anti-tumor effects, but IgG-producing B cells decreased in various tumors. Considering the underlying mechanism, 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
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