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Journal of Autoimmunity

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https://www.readbyqxmd.com/read/28919255/sumo-proteins-guardians-of-immune-system
#1
REVIEW
Sabrina Adorisio, Alessandra Fierabracci, Isabella Muscari, Anna Marina Liberati, Emira Ayroldi, Graziella Migliorati, Trinh Thi Thuy, Carlo Riccardi, Domenico V Delfino
Small ubiquitin-like modifier (SUMO) proteins belong to the ubiquitin-like family and act to change the function of target proteins through post-translational modifications. Through their interactions with innate immune pathways, SUMOs promote an efficient immune response to pathogenic challenge avoiding, at the same time, an excess of immune response that could lead to the development of autoimmune diseases. This report discusses the general functions of SUMO proteins; highlights SUMO involvement in the innate immune response through their role in NF-κB and interferon pathways; the involvement of SUMO proteins in autoimmune diseases; and reviews bacterial, viral, and parasitic interactions with SUMO pathways...
September 14, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28886898/the-differential-organogenesis-and-functionality-of-two-liver-draining-lymph-nodes-in-mice
#2
Jiali Yu, Yongyan Chen, Yuzhang Wu, Lilin Ye, Zhexiong Lian, Haiming Wei, Rui Sun, Zhigang Tian
The liver is an immunological organ. However, fundamental knowledge concerning liver-draining lymph nodes (LNs), which have been newly identified in mice as the portal and celiac LNs, is still lacking. Here, we revealed that the portal LN and celiac LN drain liver lymph through different lymphatic vessels. Although both the portal LN and celiac LN possess typical structures, they have different cell compositions. Interestingly, these two LNs form at different times during fetal development. Moreover, the organogenesis of the celiac LN, but not the portal LN, is controlled by the transcription factor NFIL3...
September 5, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28870527/identification-and-phenotyping-of-circulating-autoreactive-proteinase-3-specific-b-cells-in-patients-with-pr3-anca-associated-vasculitis-and-healthy-controls
#3
Divi Cornec, Alvise Berti, Amber Hummel, Tobias Peikert, Jacques-Olivier Pers, Ulrich Specks
OBJECTIVES: To develop a method to detect and phenotype circulating proteinase 3 (PR3)-specific B-cells in patients with PR3-ANCA associated vasculitis (AAV). METHODS: Recombinant human PR3 (rPR3) was tagged with FITC or biotin, and its binding characteristics were studied by flow cytometry using three hybridoma cell lines secreting antibodies (Ab) against human PR3, mouse PR3 (no cross-reactivity with human PR3), and human neutrophil elastase. We measured the proportion of PR3-specific B-cells and studied their surface phenotype in patients with PR3-AAV and healthy controls (HC)...
September 1, 2017: Journal of Autoimmunity
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
#4
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/28843422/redirecting-t-cells-with-chimeric-antigen-receptor-car-for-the-treatment-of-childhood-acute-lymphoblastic-leukemia
#5
REVIEW
Andrea Biondi, Chiara F Magnani, Sarah Tettamanti, Giuseppe Gaipa, Ettore Biagi
Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Nowadays the survival rate is around 85%. Nevertheless, an urgent clinical need is still represented by primary refractory and relapsed patients who do not significantly benefit from standard approaches, including chemo-radiotherapy and hematopoietic stem cell transplantation (HSCT). For this reason, immunotherapy has so far represented a challenging novel treatment opportunity, including, as the most validated therapeutic options, cancer vaccines, donor-lymphocyte infusions and tumor-specific immune effector cells...
August 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28830653/recombinant-human-igg1-based-fc-multimers-with-limited-fcr-binding-capacity-can-effectively-inhibit-complement-mediated-disease
#6
Haoping Sun, Henrik S Olsen, Emmanuel Y Mérigeon, Edward So, Erin Burch, Susan Kinsey, John C Papadimitriou, Cinthia B Drachenberg, Søren M Bentzen, David S Block, Scott E Strome, Xiaoyu Zhang
There is a lack of effective targeted therapies for the treatment of complement dependent diseases. We developed two recombinant Fc multimers, G207 and G211, with limited ability to interact with low/moderate affinity FcγRs, but with high avidity for C1q. These drugs effectively inhibited complement dependent cytotoxicity (CDC) in vitro, and prevented the deposition of C1q, C3b and MAC, on the surface of Ab-opsonized cells. Importantly, these inhibitory effects were both C1q dependent and independent. In order to determine the biologic relevance of our findings, we evaluated the clinical efficacy of these drugs in three different animal models, acute RBC hemolysis, anti-Thy-1 nephritis and passive Heymann's nephropathy (PHN), in which disease pathophysiology relies preferentially on complement activation...
August 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28803690/new-insights-into-non-conventional-epitopes-as-t-cell-targets-the-missing-link-for-breaking-immune-tolerance-in-autoimmune-disease
#7
REVIEW
James Harbige, Martin Eichmann, Mark Peakman
The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases...
August 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28774715/dendritic-cell-recruitment-and-activation-in-autoimmunity
#8
REVIEW
Silvano Sozzani, Annalisa Del Prete, Daniela Bosisio
Dendritic cells (DCs) are professional antigen presenting cells displaying the unique capability to activate naïve T cells. DCs react to pathogen encounter also by the production of mediators of inflammation, including pro-inflammatory cytokines. Because of this complex role, any imbalance in DC function reflects into defective or exaggerated immune response and tissue damage. DCs comprise two main subsets, namely conventional or classical DCs (cDCs), that are dedicated antigen presenting cells, and plasmacytoid DCs (pDCs), that respond to nucleic acids by releasing high amounts of type I interferons (IFNs)...
July 31, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28757133/corrigendum-to-autophagy-linked-fyve-containing-protein-wdfy3-interacts-with-traf6-and-modulates-rankl-induced-osteoclastogenesis-j-autoimmun-73c-2016-73-84
#9
Dennis J Wu, Ran Gu, Ritu Sarin, Regina Zavodovskaya, Chia-Pei Chen, Blaine A Christiansen, Konstantinos S Zarbalis, Iannis E Adamopoulos
No abstract text is available yet for this article.
July 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28755952/are-humans-prone-to-autoimmunity-implications-from-evolutionary-changes-in-hominin-sialic-acid-biology
#10
REVIEW
Ajit Varki
Given varied intrinsic and extrinsic challenges to the immune system, it is unsurprising that each evolutionary lineage evolves distinctive features of immunoreactivity, and that tolerance mechanisms fail, allowing autoimmunity. Humans appear prone to many autoimmune diseases, with mechanisms both genetic and environmental. Another rapidly evolving biological system involves sialic acids, a family of monosaccharides that are terminal caps on cell surface and secreted molecules of vertebrates, and play multifarious roles in immunity...
July 26, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28747257/cells-with-treg-specific-foxp3-demethylation-but-low-cd25-are-prevalent-in-autoimmunity
#11
Ricardo C Ferreira, Henry Z Simons, Whitney S Thompson, Daniel B Rainbow, Xin Yang, Antony J Cutler, Joao Oliveira, Xaquin Castro Dopico, Deborah J Smyth, Natalia Savinykh, Meghavi Mashar, Tim J Vyse, David B Dunger, Helen Baxendale, Anita Chandra, Chris Wallace, John A Todd, Linda S Wicker, Marcin L Pekalski
Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3(+) cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3(+) cells within CD127(low)CD25(low) CD4(+) T cells (here defined as CD25(low)FOXP3(+) T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes...
July 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28739356/development-of-autoantibodies-precedes-clinical-manifestations-of-autoimmune-diseases-a-comprehensive-review
#12
REVIEW
Wen-Tao Ma, Christopher Chang, M Eric Gershwin, Zhe-Xiong Lian
The etiology of autoimmune diseases is due to a combination of genetic predisposition and environmental factors that alter the expression of immune regulatory genes through various mechanisms including epigenetics. Both humoral and cellular elements of the adaptive immune system play a role in the pathogenesis of autoimmune diseases and the presence of autoantibodies have been detected in most but not all autoimmune diseases before the appearance of clinical symptoms. In some cases, the presence or levels of these autoantibodies portends not only the risk of developing a corresponding autoimmune disease, but occasionally the severity as well...
July 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28733125/modulation-of-inflammatory-and-immune-responses-by-vitamin-d
#13
REVIEW
Francesco Colotta, Birger Jansson, Fabrizio Bonelli
Vitamin D (VitD) is a prohormone most noted for the regulation of calcium and phosphate levels in circulation, and thus of bone metabolism. Inflammatory and immune cells not only convert inactive VitD metabolites into calcitriol, the active form of VitD, but also express the nuclear receptor of VitD that modulates differentiation, activation and proliferation of these cells. In vitro, calcitriol upregulates different anti-inflammatory pathways and downregulates molecules that activate immune and inflammatory cells...
July 18, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28728794/myeloid-suppressor-cells-in-cancer-and-autoimmunity
#14
REVIEW
Antonio Sica, Marco Massarotti
A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells proliferate. Cancers harness the immune regulatory mechanism that prevents autoimmunity from evading immunosurveillance and promoting immune destruction. Regulatory T cells, myeloid suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with cancer cells and causing the subversion of anti-tumor immunity. This redundant immunosuppressive network poses an impediment to efficacious immunotherapy by facilitating tumor progression...
July 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28724503/twenty-five-years-of-gene-therapy-for-genetic-diseases-and-leukemia-the-road-to-marketing-authorization-of-the-first-ex%C3%A2-vivo-gene-therapies
#15
REVIEW
Claudio Bordignon
No abstract text is available yet for this article.
July 16, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28711286/novel-therapeutic-targets-for-inflammatory-bowel-disease
#16
REVIEW
Marjorie Argollo, Gionata Fiorino, Pieter Hindryck, Laurent Peyrin-Biroulet, Silvio Danese
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are immune mediated conditions associated with progressive damage of the inflamed gut tissue, and have a considerable impact on the patient's quality of life. The pathogenesis remains uncertain, but it is clear that complex mechanisms associated with host and luminal factors are involved, generating an unbalance between pro- and anti-inflammatory signaling. It is well established that the purpose of an adequate and complete control of the intestinal inflammation measured not only by clinical symptoms, but also with more objective data such as fecal biomarkers (calprotectin) and endoscopy...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28711285/anti-il-21-monoclonal-antibody-combined-with-liraglutide-effectively-reverses-established-hyperglycemia-in-mouse-models-of-type-1-diabetes
#17
Anna K Rydén, Nikole R Perdue, Philippe P Pagni, Claire B Gibson, Sowbarnika S Ratliff, Rikke K Kirk, Travis J Friesen, Claus Haase, Ken Coppieters, Matthias G von Herrath, Tamar E Boursalian
Immunotherapy for type 1 diabetes (T1D) has previously focused on suppressing the autoimmune response against pancreatic beta cells to preserve endogenous insulin production and regulate glucose levels. With increased attention toward combination therapy strategies, studies indicate the multifunctional cytokine interleukin-21 (IL-21) may be a suitable target as an immuno-modulatory arm, while glucagon-like peptide-1 receptor (GLP-1R) agonists may be appropriate as a beta cell protective arm in combination therapy for T1D...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28709726/induction-and-maintenance-of-regulatory-t-cells-by-transcription-factors-and-epigenetic-modifications
#18
REVIEW
Mana Iizuka-Koga, Hiroko Nakatsukasa, Minako Ito, Takashi Akanuma, Qianjin Lu, Akihiko Yoshimura
Regulatory T cells (Tregs) are an essential cell subset for the maintenance of immune homeostasis. Foxp3 (Forkhead box P3) is the Treg master gene which is essential for immune suppressing activity. In addition, Tregs are characterized by a distinct pattern of gene expression, including upregulation of immune-suppressive genes and silencing of inflammatory genes. The molecular mechanisms of Treg development and maintenance have been intensively investigated. Tregs are characterized by expression of the transcription factor Foxp3...
July 11, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28701277/the-epigenetic-architecture-at-gene-promoters-determines-cell-type-specific-lps-tolerance
#19
Kerstin Klein, Mojca Frank-Bertoncelj, Emmanuel Karouzakis, Renate E Gay, Christoph Kolling, Adrian Ciurea, Nagihan Bostanci, Georgios N Belibasakis, Lih-Ling Lin, Oliver Distler, Steffen Gay, Caroline Ospelt
Synovial fibroblasts (SF) drive inflammation and joint destruction in chronic arthritis. Here we show that SF possess a distinct type of LPS tolerance compared to macrophages and other types of fibroblasts. In SF and dermal fibroblasts, genes that were non-tolerizable after repeated LPS stimulation included pro-inflammatory cytokines, chemokines and matrix metalloproteinases, whereas anti-viral genes were tolerizable. In macrophages, all measured genes were tolerizable, whereas in gingival and foreskin fibroblasts these genes were non-tolerizable...
July 9, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28689639/regulation-of-inflammation-by-members-of-the-formyl-peptide-receptor-family
#20
REVIEW
Keqiang Chen, Zhiyao Bao, Wanghua Gong, Peng Tang, Teizo Yoshimura, Ji Ming Wang
Inflammation is associated with a variety of diseases. The hallmark of inflammation is leukocyte infiltration at disease sites in response to pathogen- or damage-associated chemotactic molecular patterns (PAMPs and MAMPs), which are recognized by a superfamily of seven transmembrane, Gi-protein-coupled receptors (GPCRs) on cell surface. Chemotactic GPCRs are composed of two major subfamilies: the classical GPCRs and chemokine GPCRs. Formyl-peptide receptors (FPRs) belong to the classical chemotactic GPCR subfamily with unique properties that are increasingly appreciated for their expression on diverse host cell types and the capacity to interact with a plethora of chemotactic PAMPs and MAMPs...
July 6, 2017: Journal of Autoimmunity
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