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https://www.readbyqxmd.com/read/28926431/epigenetic-regulation-of-dendritic-cell-development-and-function
#1
Yuanyuan Tian, Lijun Meng, Yi Zhang
The immune system is characterized by the generation of structurally and functionally heterogeneous immune cells that constitute complex innate and adaptive immunity. This heterogeneity of immune cells results from changes in the expression of genes without altering DNA sequence. To achieve this heterogeneity, immune cells orchestrate the expression and functional status of transcription factor (TF) networks, which can be broadly categorized into 3 classes: pioneer TFs that facilitate initial commitment and differentiation of hematopoietic cells, subset-specific TFs that promote the generation of selected cell lineages, and immune-signaling TFs that regulate specialized function in differentiated cells...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28916112/a-novel-mimovirus-encoding-chga10-19-peptide-with-pd-l1-induces-t-cell-tolerance-and-ameliorates-the-severity-of-diabetes
#2
Hong Sun, Xiaoguang Han, Xiuhui Yan, Jingli Xu, Qiujing Huang, Fanqing Meng, Hongjin Zhang, Shufa Li
Related studies demonstrate that type 1 diabetes (T1D) is caused by β-cell antigen specific autoreactive CD8+ T cells. ChgA has recently been identified as the autoantigen in NOD mice and T1D patients. Therefore, attenuating the activation of ChgA specific CD8+ T cells might be a promising target for T1D therapy. The negative co-stimulatory PD-L1 inhibits T cell mediated alloimmunity and induces tolerance. In this experiment, a novel mimovirus encoding ChgA10-19 peptide with PD-L1 was constructed. The NOD...
September 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28899929/pathogen-specific-b-cell-receptors-drive-chronic-lymphocytic-leukemia-by-light-chain-dependent-cross-reaction-with-autoantigens
#3
Nereida Jiménez de Oya, Marco De Giovanni, Jessica Fioravanti, Rudolf Übelhart, Pietro Di Lucia, Amleto Fiocchi, Stefano Iacovelli, Dimitar G Efremov, Federico Caligaris-Cappio, Hassan Jumaa, Paolo Ghia, Luca G Guidotti, Matteo Iannacone
Several lines of evidence indirectly suggest that antigenic stimulation through the B-cell receptor (BCR) supports chronic lymphocytic leukemia (CLL) development. In addition to self-antigens, a number of microbial antigens have been proposed to contribute to the selection of the immunoglobulins expressed in CLL. How pathogen-specific BCRs drive CLL development remains, however, largely unexplored. Here, we utilized mouse models of CLL pathogenesis to equip B cells with virus-specific BCRs and study the effect of antigen recognition on leukemia growth...
September 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28887948/psoriasis-pathogenesis-and-the-development-of-novel-targeted-immune-therapies
#4
REVIEW
Jason E Hawkes, Tom C Chan, James G Krueger
Psoriasis is caused by a complex interplay between the immune system, psoriasis-associated susceptibility loci, autoantigens, and multiple environmental factors. Over the last 2 decades, research has unequivocally shown that psoriasis represents a bona fide T cell-mediated disease primarily driven by pathogenic T cells that produce high levels of IL-17 in response to IL-23. The discovery of the central role for the IL-23/type 17 T-cell axis in the development of psoriasis has led to a major paradigm shift in the pathogenic model for this condition...
September 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28887824/structural-proteins-of-the-dermal-epidermal-junction-targeted-by-autoantibodies-in-pemphigoid-diseases
#5
REVIEW
Stephanie Goletz, Detlef Zillikens, Enno Schmidt
The dermal-epidermal junction consists of a network of several interacting structural proteins which strengthen adhesion and mediate signaling events. This structural network consists of hemidesmosomal-anchoring filament complexes connecting the basal keratinocytes to the basement membrane. The anchoring filaments in turn interact with the anchoring fibrils to attach the basement membrane to the underlying dermis. Several of these structural proteins are recognized by autoantibodies in pemphigoid diseases, a heterogeneous group of clinically and immunopathologically diverse entities...
September 8, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28886485/development-of-an-epitope-based-vaccine-inhibiting-immune-cells-rolling-and-migration-against-atherosclerosis-using-in-silico-approaches
#6
Mehdi Tourani, Ahmad Karkhah, Ali Najafi
Atherosclerosis is a chronic inflammatory disease characterized by formation of pro-oxidative lipids in large and medium-sized vessels. Over the years, many treatments and drugs have entered the market to improve atherosclerosis and autoantigen-mediated active immunization is currently considered as a beneficial method. Therefore, this study was conducted to design a novel epitope-based vaccine against atherosclerosis employing CD99, CD81 and CD99L2 antigens. In this way, structural vaccinology approaches were used to design a novel multi-epitope vaccine against atherosclerosis...
September 1, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28880680/the-effect-and-possible-clinical-efficacy-of-in-vivo-inhibition-of-neutrophil-extracellular-traps-by-blockade-of-pi3k-gamma-on-the-pathogenesis-of-microscopic-polyangiitis
#7
Hirotaka Kimura, Yasushi Matsuyama, Sachiko Araki, Atsushi Koizumi, Yumi Kariya, Shunsuke Takasuga, Satoshi Eguchi, Hiroki Nakanishi, Junko Sasaki, Takehiko Sasaki
OBJECTIVE: Neutrophil extracellular traps (NETs) are peculiar structures composed of the externalized chromatin with intracellular proteins and formed by activated neutrophils in a reactive oxygen species (ROS)-dependent manner. Aberrant NETs are considered to be autoantigens for anti-neutrophil cytoplasmic antibodies (ANCAs) underling the development of microscopic polyangiitis (MPA). However, little is known regarding the therapeutic efficacy of in vivo inhibition of NET formation (NETosis) on MPA pathogenesis...
September 7, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28879482/pristane-induced-lupus-considerations-on-this-experimental-model
#8
Eduarda Correa Freitas, Mayara Souza de Oliveira, Odirlei André Monticielo
Systemic lupus erythematosus (SLE) is a multifactorial, autoimmune inflammatory disease with pleomorphic clinical manifestations involving different organs and tissues. The etiology of this disease has been associated with a dysfunctional response of B and T lymphocytes against environmental stimuli in individuals genetically susceptible to SLE, which determines an immune response against different autoantigens and, consequently, tissue damage. The study of different murine models has provided a better understanding of these autoimmune phenomena...
September 6, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28877470/strong-clonal-relatedness-between-serum-and-gut-iga-despite-different-plasma-cell-origins
#9
Rasmus Iversen, Omri Snir, Maria Stensland, José E Kroll, Øyvind Steinsbø, Ilma R Korponay-Szabó, Knut E A Lundin, Gustavo A de Souza, Ludvig M Sollid
Mucosal antigens induce generation of lamina propria plasma cells (PCs) that secrete dimeric immunoglobulin A (IgA) destined for transport across the epithelium. In addition, blood contains monomeric IgA. To study the relationship between mucosal and systemic antibody responses, we took advantage of celiac disease patient samples for isolation of gut PCs as well as serum IgA and IgG reactive with a gluten-derived peptide or the autoantigen transglutaminase 2. Proteomic analysis of serum IgA revealed antigen-specific V-gene preferences, which matched those found in gut PCs...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28874533/type-1-diabetes-induction-in-humanized-mice
#10
Shulian Tan, Yang Li, Jinxing Xia, Chun-Hui Jin, Zheng Hu, Gaby Duinkerken, Yuying Li, Mohsen Khosravi Maharlooei, Estefania Chavez, Grace Nauman, Nichole Danzl, Maki Nakayama, Bart O Roep, Megan Sykes, Yong-Guang Yang
There is an urgent and unmet need for humanized in vivo models of type 1 diabetes to study immunopathogenesis and immunotherapy, and in particular antigen-specific therapy. Transfer of patient blood lymphocytes to immunodeficient mice is associated with xenogeneic graft-versus-host reactivity that complicates assessment of autoimmunity. Improved models could identify which human T cells initiate and participate in beta-cell destruction and help define critical target islet autoantigens. We used humanized mice (hu-mice) containing robust human immune repertoires lacking xenogeneic graft-versus-host reactivity to address this question...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28872459/mir-146a-modulates-autoreactive-th17-cell-differentiation-and-regulates-organ-specific-autoimmunity
#11
Bo Li, Xi Wang, In Young Choi, Yu-Chen Wang, Siyuan Liu, Alexander T Pham, Heesung Moon, Drake J Smith, Dinesh S Rao, Mark P Boldin, Lili Yang
Autoreactive CD4 T cells that differentiate into pathogenic Th17 cells can trigger autoimmune diseases. Therefore, investigating the regulatory network that modulates Th17 differentiation may yield important therapeutic insights. miR-146a has emerged as a critical modulator of immune reactions, but its role in regulating autoreactive Th17 cells and organ-specific autoimmunity remains largely unknown. Here, we have reported that miR-146a-deficient mice developed more severe experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS)...
September 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28872108/induction-of-paralysis-and-visual-system-injury-in-mice-by-t-cells-specific-for-neuromyelitis-optica-autoantigen-aquaporin-4
#12
Sharon A Sagan, Andrés Cruz-Herranz, Collin M Spencer, Peggy P Ho, Lawrence Steinman, Ari J Green, Raymond A Sobel, Scott S Zamvil
While it is recognized that aquaporin-4 (AQP4)-specific T cells and antibodies participate in the pathogenesis of neuromyelitis optica (NMO), a human central nervous system (CNS) autoimmune demyelinating disease, creation of an AQP4-targeted model with both clinical and histologic manifestations of CNS autoimmunity has proven challenging. Immunization of wild-type (WT) mice with AQP4 peptides elicited T cell proliferation, although those T cells could not transfer disease to naïve recipient mice. Recently, two novel AQP4 T cell epitopes, peptide (p) 135-153 and p201-220, were identified when studying immune responses to AQP4 in AQP4-deficient (AQP4(-/-)) mice, suggesting T cell reactivity to these epitopes is normally controlled by thymic negative selection...
August 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28864875/deciphering-the-pathogenesis-of-human-type-1-diabetes-t1d-by-interrogating-t-cells-from-the-scene-of-the-crime
#13
REVIEW
Sally C Kent, Stuart I Mannering, Aaron W Michels, Jenny Aurielle B Babon
PURPOSE OF REVIEW: Autoimmune-mediated destruction of insulin-producing β-cells within the pancreas results in type 1 diabetes (T1D), which is not yet preventable or curable. Previously, our understanding of the β-cell specific T cell repertoire was based on studies of autoreactive T cell responses in the peripheral blood of patients at risk for, or with, T1D; more recently, investigations have included immunohistochemical analysis of some T cell specificities in the pancreas from organ donors with T1D...
September 2, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28864263/mechanism-of-chimeric-vaccine-stimulation-of-indoleamine-2-3-dioxygenase-biosynthesis-in-human-dendritic-cells-is-independent-of-tgf-%C3%AE-signaling
#14
Grace E Esebanmen, William H R Langridge
Cholera toxin B subunit fusion to autoantigens such as proinsulin (CTB-INS) down regulate dendritic cell (DC) activation and stimulate synthesis of DC immunosuppressive cytokines. Recent studies of CTB-INS induction of immune tolerance in human DCs indicate that increased biosynthesis of indoleamine 2,3-dioxygenase (IDO1) may play an important role in CTB-INS vaccine suppression of DC activation. Studies in murine models suggest a role for transforming growth factor beta (TGF-β) in the stimulation of IDO1 biosynthesis, for the induction of tolerance in DCs...
August 21, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28861084/autoantibody-repertoire-in-apeced-patients-targets-two-distinct-subgroups-of-proteins
#15
Dmytro Fishman, Kai Kisand, Christina Hertel, Mike Rothe, Anu Remm, Maire Pihlap, Priit Adler, Jaak Vilo, Aleksandr Peet, Antonella Meloni, Katarina Trebusak Podkrajsek, Tadej Battelino, Øyvind Bruserud, Anette S B Wolff, Eystein S Husebye, Nicolas Kluger, Kai Krohn, Annamari Ranki, Hedi Peterson, Adrian Hayday, Pärt Peterson
High titer autoantibodies produced by B lymphocytes are clinically important features of many common autoimmune diseases. APECED patients with deficient autoimmune regulator (AIRE) gene collectively display a broad repertoire of high titer autoantibodies, including some which are pathognomonic for major autoimmune diseases. AIRE deficiency severely reduces thymic expression of gene-products ordinarily restricted to discrete peripheral tissues, and developing T cells reactive to those gene-products are not inactivated during their development...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28861003/nanobubbles-form-at-active-hydrophobic-spots-on-the-luminal-aspect-of-blood-vessels-consequences-for-decompression-illness-in-diving-and-possible-implications-for-autoimmune-disease-an-overview
#16
REVIEW
Ran Arieli
Decompression illness (DCI) occurs following a reduction in ambient pressure. Decompression bubbles can expand and develop only from pre-existing gas micronuclei. The different hypotheses hitherto proposed regarding the nucleation and stabilization of gas micronuclei have never been validated. It is known that nanobubbles form spontaneously when a smooth hydrophobic surface is submerged in water containing dissolved gas. These nanobubbles may be the long sought-after gas micronuclei underlying decompression bubbles and DCI...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28855257/the-molecular-basis-for-peptide-repertoire-selection-in-the-human-leucocyte-antigen-hla-c-06-02-molecule
#17
Jesse I Mobbs, Patricia T Illing, Nadine L Dudek, Andrew G Brooks, Daniel G Baker, Anthony W Purcell, Jamie Rossjohn, Julian P Vivian
Human Leucocyte antigen (HLA) C*06:02 is identified as the allele associated with the highest risk for the development of the autoimmune skin disease psoriasis. However, the diversity and mode of peptide presentation by the HLA-C*06:02 molecule remains unclear. Here, we describe the endogenous peptide repertoire of approximately 3,000 sequences for HLA-C*06:02 that defines the peptide-binding motif for this HLA allomorph. We found that HLA-C*06:02 predominantly presents nonamer peptides with dominant arginine anchors at the P2 & P7 positions and a preference for small hydrophobic residues at the C-terminus (Pomega)...
August 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28844827/beh%C3%A3-et-disease-serum-is-immunoreactive-to-neurofilament-medium-which-share-common-epitopes-to-bacterial-hsp-65-a-putative-trigger
#18
S Lule, A I Colpak, B Balci-Peynircioglu, Y Gursoy-Ozdemir, S Peker, U Kalyoncu, A Can, N Tekin, D Demiralp, T Dalkara
Autoimmune and dysimmune inflammatory mechanisms on a genetically susceptible background are implicated in the etiology of Behçet's Disease (BD). Heat-shock protein-65 (HSP-65) derived from Streptococcus sanguinis was proposed as a triggering factor based on its homology with human HSP-60. However, none of the autoantigens identified so far in sera from BD share common epitopes with bacterial HSP-65 or has a high prevalence. Here, we report that sera from BD patients are immunoreactive against filamentous neuronal processes in the mouse brain, retina and scrotal skin in great majority of patients...
August 24, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28840564/human-leukemia-antigen-a-0201-restricted-epitopes-of-human-endogenous-retrovirus-w-family-envelope-herv-w-env-induce-strong-cytotoxic-t-lymphocyte-responses
#19
Xiaoning Tu, Shan Li, Lijuan Zhao, Ran Xiao, Xiuling Wang, Fan Zhu
Human endogenous retrovirus W family (HERV-W) envelope (env) has been reported to be related to several human diseases, including autoimmune disorders, and it could activate innate immunity. However, there are no reports investigating whether human leukemia antigen (HLA)-A*0201(+) restriction is involved in the immune response caused by HERV-W env in neuropsychiatric diseases. In the present study, HERV-W env-derived epitopes presented by HLA-A*0201 are described with the potential for use in adoptive immunotherapy...
August 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28838943/zaimoku-y-takamatsu-h-hosomichi-k-et-al-identification-of-an-hla-class-i-allele-closely-involved-in-the-autoantigen-presentation-in-acquired-aplastic-anemia-blood-2017-129-21-2908-2916
#20
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