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Andrew J McDermott, Bruce S Klein
The mucosal surface of the respiratory tract encounters microbes, such as fungal particles, with every inhaled breath. When pathogenic fungi breach the physical barrier and innate immune system within the lung to establish an infection, adaptive immunity is engaged often in the form of helper CD4 T-cell responses. Type 1 responses, characterized by IFNγ production from CD4 cells, promote clearance of Histoplasma capsulatum and Cryptococcus neoformans infection. Likewise, IL-17A production from Th17 cells promotes immunity to Blastomyces dermatitidis and Coccidiodes species infection by recruiting neutrophils...
May 20, 2018: Immunology
Lee I Garner, Andrew Hartland, Johannes Breuning, Marion H Brown
CD6 is a type I T cell surface receptor which modulates antigen receptor signalling. Its activity is regulated by binding of its membrane proximal domain (domain 3) to a cell surface ligand, CD166. CD6 monoclonal antibodies (mAbs) specific for the membrane distal domain (domain 1) perturb CD6 function including itolizumab (Alzumab™ ) which has reached the clinic for treatment of autoimmune disease. We characterised molecular and functional properties of several CD6 mAbs including itolizumab to define potential mechanisms of action...
May 17, 2018: Immunology
Muzamil Y Want, Amit A Lugade, Sebastiano Battaglia, Kunle Odunsi
Major progress in the analysis of human immune responses to cancer has been made through the molecular characterization of human tumor antigens. The development of therapeutic strategies for eliciting immune-mediated rejection of tumors has accelerated due to the elucidation of the molecular basis for tumor cell recognition and destruction by immune cells. Of the various human tumor antigens defined to date in ovarian cancer, the cancer-testis (CT) family of antigens have studied extensively pre-clinically and clinically due their testis-restricted expression in normal tissues and ability to elicit robust immune responses...
May 17, 2018: Immunology
Kyle L Flannigan, Timothy L Denning
Segmented filamentous bacteria (SFB) are gram-positive, spore-forming, bacteria that primarily colonize the ileum of the small intestine. Upon direct adherence to intestinal epithelial cells, SFB actively stimulate innate and adaptive immune cell activation. The cardinal features of SFB-induced gut immunity - Th17 cell differentiation, IgA production, and barrier protection - lead to the containment of SFB and further afford protection against invading pathogens. Th17 cells and IL-17A, however, can also reach peripheral sites and exacerbate autoimmunity...
May 17, 2018: Immunology
Rong Yang, Ting-Ting Cai, Xiao-Jun Wu, Yi-Na Liu, Jia He, Xiao-Shi Zhang, Gang Ma, Jiang Li
The expansion of myeloid-derived suppressor cells (MDSCs) correlates with tumorigenesis in colorectal cancer (CRC). Here, we found a significant association between CD33+ MDSC number and YAP1 and PTEN levels in CRC patients (P < 0.05). Moreover, the CD33+ MDSCs, YAP1 and PTEN were identified as predictors for the prognosis of CRC patients (P < 0.05). Notably, CD33+ MDSCs were an independent survival predictor for CRC patients through a Cox model analysis. In vitro data determined that the expression levels of YAP1 and PTEN in CRC-derived cell lines were associated with CRC-derived MDSC induction, and the blockade of YAP1 and PTEN decreased CRC-derived MDSC induction...
May 16, 2018: Immunology
Jennifer Y Barr, Xiaofang Wang, Portia A Kreiger, Scott M Lieberman
Immune cell-mediated destruction of salivary glands is a hallmark feature of Sjögren syndrome. Similar to the female predominance in humans, female nonobese diabetic (NOD) mice develop spontaneous salivary gland autoimmunity. However, in both humans and mice it is unclear what factors contribute to the initial immune infiltration of the salivary glands. Here, we used an adoptive transfer model of Sjögren syndrome to determine if female mice harbor a sex-specific defect in salivary gland-protective regulatory T (Treg) cells...
May 11, 2018: Immunology
Mariah L Hoye, Angela S Archambault, Taylor M Gordon, Landon K Oetjen, Matthew D Cain, Robyn S Klein, Seth D Crosby, Brian S Kim, Timothy M Miller, Gregory F Wu
Innate immune cells are integral to the pathogenesis of several diseases of the central nervous system (CNS), including multiple sclerosis (MS). Dendritic cells (DCs) are potent CD11c+ antigen-presenting cells that are critical regulators of adaptive immune responses, particularly in autoimmune diseases such as MS. The regulation of DC function in both the periphery and CNS compartment has not been fully elucidated. One limitation to studying the role of CD11c+ DCs in the CNS is that microglia can upregulate CD11c during inflammation, making it challenging to distinguish bone marrow-derived DCs (BMDCs) from microglia...
May 10, 2018: Immunology
Penelope A Morel
Upon encounter with their cognate antigen naïve CD4 T cells become activated and are induced to differentiate into several possible T helper (Th) cell subsets. This differentiation depends on a number of factors including antigen presenting cells, cytokines and costimulatory molecules. The strength of the T cell receptor (TCR) signal, related to the affinity of TCR for antigen and antigen dose, has emerged as a dominant factor in determining Th cell fate. Recent studies have revealed that TCR signals of high or low strength do not simply induce quantitatively different signals in the T cells, but rather qualitatively distinct pathways can be induced based on TCR signal strength...
May 2, 2018: Immunology
Larissa M S Martins, Malena M Perez, Camila A Pereira, Frederico R C Costa, Murilo S Dias, Rita C Tostes, Simone G Ramos, Marcel R de Zoete, Bernhard Ryffel, João S Silva, Daniela Carlos
We addressed the role of IL-23 in driving the intestinal Th17 response during obesity and metabolic syndrome progression induced by a high-fat diet (HFD). Diet-induced obese (DIO) and lean mice received HFD or control diet (CTD), respectively, for 20 weeks. The nutritional, metabolic and immune parameters were examined at weeks 9 and 20. Gene and protein IL-23p19 and IL-23R expression was increased in the ileum of obese wild-type mice (WT) fed the HFD for nine weeks. Mice lacking IL-23 and fed the HFD exhibited greater weight gain, higher fat accumulation, adipocyte hypertrophy and hepatic steatosis...
May 2, 2018: Immunology
Matthias Schaier, Angele Leick, Lorenz Uhlmann, Florian Kälble, Christian Morath, Volker Eckstein, Anthony Ho, Carsten Mueller-Tidow, Stefan Meuer, Karsten Mahnke, Claudia Sommerer, Martin Zeier, Andrea Steinborn
Premature aging of both CD4+ -regulatory- (Tregs) and CD4+ -responder-T-cells (Tresps) in end-stage renal disease (ESRD) patients is expected to affect the success of later kidney transplantation. Both T-cell populations are released from the thymus as inducible co-stimulatory (ICOS+ -) and ICOS- -recent thymic emigrant (RTE)-Tregs/Tresps, which differ primarily in their proliferative capacities. In this study, we analysed the effect of ESRD and subsequent renal replacement therapies on the differentiation of ICOS+ - and ICOS- -RTE-Tregs/Tresps into ICOS+ - or ICOS- -CD31- -Memory-Tregs/Tresps and examined whether diverging pathways affected the suppressive activity of ICOS+ - and ICOS- -Tregs in co-culture with autologous Tresps...
May 2, 2018: Immunology
Damien Chaussabel, Darawan Rinchai
Systems-scale molecular profiling data accumulating in public repositories may constitute a useful resource for immunologists. For instance, datasets which are directly relevant to their respective line of research are likely to be found among the more than 90,000 data series available in the NCBI Gene Expression Omnibus. Such "collective omics data" may also be employed as source material for training purposes. This is the case when training curriculums aim at the development of bioinformatics skills necessary for the analysis, interpretation or visualization of data generated on global scales...
April 28, 2018: Immunology
Kunal Dhume, K Kai McKinstry
CD4 T cells contribute to protection against pathogens through numerous mechanisms. Incorporating the goal of memory CD4 T cell generation into vaccine strategies thus offers a powerful approach to improve their efficacy, especially in situations where humoral responses alone cannot confer long-term immunity. These threats include viruses such as influenza that mutate coat proteins to avoid neutralizing antibodies, but that are targeted by T cells that recognize more conserved protein epitopes shared by different strains...
April 27, 2018: Immunology
Tomasz Ahrends, Jannie Borst
Cancer immunotherapy focuses mainly on anti-tumor activity of CD8+ cytotoxic T lymphocytes (CTLs). CTLs can directly kill all tumor cell types, provided that they carry recognizable antigens. However, CD4+ T cells also play important roles in anti-tumor immunity. CD4+ T cells can either suppress or promote anti-tumor CTL response, both in secondary lymphoid organs or in the tumor. In this review, we highlight opposing mechanisms of conventional (Tconv) and regulatory (Treg) T cells at both sites. We outline how current cancer immunotherapy strategies affect both subsets and how selective modulation of each subset is important to maximize the clinical response of cancer patients...
April 27, 2018: Immunology
Lian-Ju Li, Zhi-Wei Zhu, Wei Zhao, Sha-Sha Tao, Bao-Zhu Li, Shu-Zhen Xu, Jie-Bing Wang, Ming-Yue Zhang, Jun Wu, Rui-Xue Leng, Yin-Guang Fan, Hai-Feng Pan, Dong-Qing Ye
Circular RNAs (circRNAs) represent as a class of non-coding RNAs which form covalently closed RNA circles, and their extensive expression and conservation in mammals are observed. CircRNAs regulate gene expression through acting as competitive endogenous RNAs (ceRNAs) and modulating gene transcription. Accumulating evidence supports the implication of circRNAs in a variety of human diseases. Yet, study exploring the role of circRNAs in systemic lupus erythematosus (SLE) is lacking. The present study measured the circRNAs expression profiles in T cells from SLE patients and healthy controls with human circRNA microarray and identified 127 differentially expressed circRNAs in SLE patients...
April 26, 2018: Immunology
Larissa S Celiberto, Franziska A Graef, Genelle R Healey, Else S Bosman, Kevan Jacobson, Laura M Sly, Bruce A Vallance
Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, thought to at least in part reflect an aberrant immune response to gut bacteria. IBD is increasing in incidence, particularly in populations that have recently immigrated to Western countries. This suggests that environmental factors are involved in its pathogenesis. We hypothesize that the increase in IBD rates might reflect the consumption of an unhealthy Western diet, containing excess calories and lacking in key nutritional factors, such as fiber and vitamin D...
April 25, 2018: Immunology
Song Zhang
Th17 cells play critical roles in inflammatory and autoimmune diseases. The lineage-specific transcription factor RORγt is the key regulator for Th17 cell fate commitment. A substantial number of studies have established the importance of TGF-β-dependent pathways in inducing RORγt expression and Th17 differentiation. TGF-β superfamily members TGF-β1, TGF-β3, or activin A, in concert with IL-6 or IL-21 differentiate naïve T cells into Th17 cells. Alternatively, Th17 differentiation can occur through TGF-β-independent pathways...
April 23, 2018: Immunology
Thomas Scambler, Jonathan Holbrook, Sinisa Savic, Michael F McDermott, Daniel Peckham
Ascertaining the dominant cell type driving an immunological disease is essential to understanding the causal pathology and, therefore, selecting or developing an effective treatment. Classifying immunological diseases in this way has led to successful treatment regimens for many monogenic diseases; however, when the dominant cell type is unclear and there is no obvious causal genetic mutation, then identifying the correct disease classification and appropriate therapy can be challenging. In this review we focus on pulmonary immunological diseases where an innate immune signature has been identified as a predominant aspect of the immunopathology...
April 19, 2018: Immunology
Lena Katharina Freudenmann, Ana Marcu, Stefan Stevanović
The entirety of HLA-presented peptides is referred to as the HLA ligandome of a cell or tissue, in tumours often termed immunopeptidome. Mapping the tumour immunopeptidome by mass spectrometry (MS) comprehensively views the pathophysiologically relevant antigenic signature of human malignancies. MS is an unbiased approach stringently filtering the candidates to be tested as opposed to epitope prediction algorithms. In the setting of peptide-specific immunotherapies, MS-based strategies significantly diminish the risk of lacking clinical benefit, as they yield highly enriched amounts of truly presented peptides...
April 15, 2018: Immunology
Lin Chen, Ye Tian, Kai Zhan, Anan Chen, Zhiming Weng, Jiao Huang, Yanyan Li, Yongjie Sun, Hongjun Zheng, Yi Li
The affinity of T cell receptor (TCR) determines the efficacy of TCR based immunotherapy. By using human leukocyte antigen (HLA)-A*02 transgenic mice, a TCR was generated previously specific for human tumor testis antigen peptide MAGE-A3112-120 (KVAELVHFL) HLA-A*02 complex. We developed an approach to humanize the murine TCR by replacing the mouse framework with sequences of folding optimized human TCR variable domains for retaining binding affinity. The resultant humanized TCR exhibited higher affinity and conferred better anti-tumor activity than its parent murine MAGE-A3 TCR (SRm1)...
April 12, 2018: Immunology
Stefanie Haase, Aiden Haghikia, Nicola Wilck, Dominik N Müller, Ralf A Linker
A vast number of studies have demonstrated a remarkable role for the gut microbiota and their metabolites in the pathogenesis of inflammatory diseases, including multiple sclerosis (MS). Recent studies in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, have revealed that modifying certain intestinal bacterial populations may influence immune cell priming in the periphery, resulting in dysregulation of immune responses and neuroinflammatory processes in the central nervous system (CNS)...
April 11, 2018: Immunology
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