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https://www.readbyqxmd.com/read/28529452/estradiol-suppresses-tlr4-triggered-apoptosis-of-decidual-stromal-cells-and-drives-an-anti-inflammatory-th2-shift-by-activating-sgk1
#1
Yiyun Lou, Minhao Hu, Qijing Wang, Mu Yuan, Ning Wang, Fang Le, Lejun Li, Shisi Huang, Liya Wang, Xiangrong Xu, Fan Jin
A pro-inflammatory cytokine profile at the feto-maternal interface may predispose immune maladaptation notably in early miscarriages. We investigated the involvement of estradiol (E2)-activated serum-glucocorticoid regulated kinase 1 (SGK1) in preserving the tolerogenic and pro-survival intrauterine microenvironment beneficial to gestation maintenance. Decidual SGK1 was down-regulated in early miscarriage, consistent with the lower serum E2 concentration seen in pregnancy loss. Lipopolysaccharide (LPS)/Toll-like receptors 4 (TLR4) signaling induced apoptosis and the pro-inflammatory T helper type (TH) 1 response of decidual stromal cells (DSCs) were associated with miscarriage...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#2
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28521905/harnessing-the-properties-of-dendritic-cells-in-the-pursuit-of-immunological-tolerance
#3
REVIEW
Christopher Horton, Kumaran Shanmugarajah, Paul J Fairchild
The acquisition of self-perpetuating, immunological tolerance specific for graft alloantigens has long been described as the "holy grail" of clinical transplantation. By removing the need for life-long immunosuppression following engraftment, the adverse consequences of immunosuppressive regimens, including chronic infections and malignancy, may be avoided. Furthermore, autoimmune diseases and allergy are, by definition, driven by aberrant immunological responses to ordinarily innocuous antigens. The re-establishment of permanent tolerance towards instigating antigens may, therefore, provide a cure to these common diseases...
April 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28521904/make-immunological-peace-not-war-potential-applications-of-tolerogenic-dendritic-cells
#4
EDITORIAL
Emma Louise Walton
In this issue of the Biomedical Journal, we explore the powerful immunosuppressive properties of tolerogenic dendritic cells and discuss their potential to bring about lifelong tolerance in transplantation and autoimmune disease. We also highlight an exciting new development in the field of malaria diagnosis that could facilitate early detection of the disease.
April 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28521316/introduction-of-complementary-foods-to-infants
#5
Christina West
While earlier food allergy prevention strategies implemented avoidance of allergenic foods in infancy, the current paradigm is shifting from avoidance to controlled exposure. This review focuses on the outcome of recent randomized controlled trials, which have examined the early introduction of allergenic foods for allergy prevention, and discusses the implementation of results in clinical practice. In infants at high risk of allergic disease, there is now direct evidence that regular early peanut consumption will reduce the prevalence of peanut allergy, compared to avoidance...
2017: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/28511837/immunomodulatory-activity-of-recombinant-%C3%AE-gliadin-conjugated-to-cholera-toxin-in-dq8-transgenic-mice
#6
Stefano Rossi, Diomira Luongo, Francesco Maurano, Paolo Bergamo, Mauro Rossi
Coeliac disease (CD) is characterized by an intestinal lesion sustained by an abnormal mucosal T-cell response to wheat gliadin. An immunological approach that is able to suppress this immune response is a perspective worth pursuing. Several strategies of antigen administration have been aimed at the downregulation of pathogenic T-cells. In particular, we previously reported a significant suppression of the systemic cell-mediated response toward wheat gliadin in DQ8 transgenic mice receiving nasally a recombinant α-gliadin...
May 13, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28505675/-anti-lymph-angiogenic-strategies-to-improve-corneal-graft-survival
#7
Felix Bock, Claus Cursiefen
Corneal transplantation (keratoplasty) is the most frequently performed form of transplantation worldwide. A rejection reaction against the transplant is the main complication occurring after transplantation in an already vascularized, so-called "high-risk" recipient eye. Our group has shown that clinically invisible lymphatic vessels play a crucial role in the induction of a rejection reaction against the corneal graft, and that anti-(lymph)angiogenic therapies in the mouse model of keratoplasty can significantly improve transplant survival...
May 2017: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/28496201/engulfment-signals-and-the-phagocytic-machinery-for-apoptotic-cell-clearance
#8
REVIEW
Seung-Yoon Park, In-San Kim
The clearance of apoptotic cells is an essential process for tissue homeostasis. To this end, cells undergoing apoptosis must display engulfment signals, such as 'find-me' and 'eat-me' signals. Engulfment signals are recognized by multiple types of phagocytic machinery in phagocytes, leading to prompt clearance of apoptotic cells. In addition, apoptotic cells and phagocytes release tolerogenic signals to reduce immune responses against apoptotic cell-derived self-antigens. Here we discuss recent advances in our knowledge of engulfment signals, the phagocytic machinery and the signal transduction pathways for apoptotic cell engulfment...
May 12, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28479234/controlled-delivery-of-single-or-multiple-antigens-in-tolerogenic-nanoparticles-using-peptide-polymer-bioconjugates
#9
Ryan M Pearson, Liam M Casey, Kevin R Hughes, Leon Z Wang, Madeleine G North, Daniel R Getts, Stephen D Miller, Lonnie D Shea
Polymeric nanoparticles (NPs) have demonstrated their potential to induce antigen (Ag)-specific immunological tolerance in multiple immune models and are at various stages of commercial development. Association of Ag with NPs is typically achieved through surface coupling or encapsulation methods. However, these methods have limitations that include high polydispersity, uncontrollable Ag loading and release, and possible immunogenicity. Here, using antigenic peptides conjugated to poly(lactide-co-glycolide), we developed Ag-polymer conjugate NPs (acNPs) with modular loading of single or multiple Ags, negligible burst release, and minimally exposed surface Ag...
May 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28468968/tolerogenic-versus-immunogenic-lipidomic-profiles-of-cd11c-immune-cells-and-control-of-immunogenic-dendritic-cell-ceramide-dynamics
#10
Carlos Ocaña-Morgner, Susanne Sales, Manuela Rothe, Andrej Shevchenko, Rolf Jessberger
Lipids affect the membrane properties determining essential biological processes. Earlier studies have suggested a role of switch-activated protein 70 (SWAP-70) in lipid raft formation of dendritic cells. We used lipidomics combined with genetic and biochemical assays to analyze the role of SWAP-70 in lipid dynamics. TLR activation using LPS as a ligand represented a pathogenic immunogenic stimulus, physical disruption of cell-cell contacts a tolerogenic stimulus. Physical disruption, but not LPS, caused an increase of phosphatidylcholine ether and cholesteryl esters in CD11c(+) immune cells...
May 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28467828/dominant-protection-from-hla-linked-autoimmunity-by-antigen-specific-regulatory-t-cells
#11
Joshua D Ooi, Jan Petersen, Yu H Tan, Megan Huynh, Zoe J Willett, Sri H Ramarathinam, Peter J Eggenhuizen, Khai L Loh, Katherine A Watson, Poh Y Gan, Maliha A Alikhan, Nadine L Dudek, Andreas Handel, Billy G Hudson, Lars Fugger, David A Power, Stephen G Holt, P Toby Coates, Jon W Gregersen, Anthony W Purcell, Stephen R Holdsworth, Nicole L La Gruta, Hugh H Reid, Jamie Rossjohn, A Richard Kitching
Susceptibility and protection against human autoimmune diseases, including type I diabetes, multiple sclerosis, and Goodpasture disease, is associated with particular human leukocyte antigen (HLA) alleles. However, the mechanisms underpinning such HLA-mediated effects on self-tolerance remain unclear. Here we investigate the molecular mechanism of Goodpasture disease, an HLA-linked autoimmune renal disorder characterized by an immunodominant CD4(+) T-cell self-epitope derived from the α3 chain of type IV collagen (α3135-145)...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28461074/vitamin-d-endocrinology-on-the-cross-road-between-immunity-and-metabolism
#12
REVIEW
An-Sofie Vanherwegen, Conny Gysemans, Chantal Mathieu
The effects of vitamin D on the immune function have been recognized for more than a quarter of a century. However, our understanding of the multifactorial nature of the effects of vitamin D at the cellular, molecular and metabolic level in different immune subsets of the innate and adaptive system has dramatically progressed during the last decades. In this review, we summarize the main metabolic pathways preferentially used in different subsets of T cells, B cells, macrophages and dendritic cells as well as the immunomodulatory effects of vitamin D on these cells...
April 28, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28459871/immunological-effects-of-reduced-mucosal-integrity-in-the-early-life-of-balb-c-mice
#13
Katja Maria Bendtsen, Camilla Hartmann Friis Hansen, Łukasz Krych, Kerstin Skovgaard, Witold Kot, Finn Kvist Vogensen, Axel Kornerup Hansen
Certain stimuli at the gut barrier may be necessary in early life to establish a proper balance of immune tolerance. We evaluated a compromised barrier in juvenile mice in relation to microbiota and local and systemic immunity. BALB/c mice were treated with a low dose of dextran sulfate sodium (DSS) with or without ampicillin and lipopolysaccharide (LPS) to clarify the importance of microbial antigens and interaction between microbial-associated patterns and toll-like receptors. The barrier breach resulted in increased plasma LPS, which was highest in mice treated simultaneously with ampicillin...
2017: PloS One
https://www.readbyqxmd.com/read/28458670/gut-microbiota-species-can-provoke-both-inflammatory-and-tolerogenic-immune-responses-in-human-dendritic-cells-mediated-by-retinoic-acid-receptor-alpha-ligation
#14
Krisztian Bene, Zsofia Varga, Viktor O Petrov, Nadiya Boyko, Eva Rajnavolgyi
Dendritic cells are considered as the main coordinators of both mucosal and systemic immune responses, thus playing a determining role in shaping the outcome of effector cell responses. However, it is still uncovered how primary human monocyte-derived DC (moDC) populations drive the polarization of helper T (Th) cells in the presence of commensal bacteria harboring unique immunomodulatory properties. Furthermore, the individual members of the gut microbiota have the potential to modulate the outcome of immune responses and shape the immunogenicity of differentiating moDCs via the activation of retinoic acid receptor alpha (RARα)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28455654/metabolically-inactive-insulin-analogue-does-not-prevent-autoimmune-diabetes-in-nod-mice
#15
Juha Grönholm, Philippe P Pagni, Minh N Pham, Claire B Gibson, Paul F Macomber, José Luis Vela, Matthias von Herrath, Michael J Lenardo
AIMS/HYPOTHESIS: Insulin is widely considered to be a driver antigen in type 1 diabetes in humans and in mouse models of the disease. Therefore, insulin or insulin analogues are candidates for tolerogenic drugs to prevent disease onset in individuals with risk of diabetes. Previous experiments have shown that autoimmune diabetes can be prevented in NOD mice by repeated doses of insulin administered via an oral, nasal or parenteral route, but clinical trials in humans have not succeeded...
April 28, 2017: Diabetologia
https://www.readbyqxmd.com/read/28448002/measurement-of-t-cell-alloreactivity-using-imaging-flow-cytometry
#16
Stephen C Juvet, Sajad Moshkelgosha, Sharon Sanderson, Joanna Hester, Kathryn J Wood, Andrew Bushell
The measurement of immunological reactivity to donor antigens in transplant recipients is likely to be crucial for the successful reduction or withdrawal of immunosuppression. The mixed leukocyte reaction (MLR), limiting dilution assays, and trans-vivo delayed-type hypersensitivity (DTH) assay have all been applied to this question, but these methods have limited predictive ability and/or significant practical limitations that reduce their usefulness. Imaging flow cytometry is a technique that combines the multiparametric quantitative powers of flow cytometry with the imaging capabilities of fluorescent microscopy...
April 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28442553/nlrp3-signaling-drives-macrophage-induced-adaptive-immune-suppression-in-pancreatic-carcinoma
#17
Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Gautam S D Balasubramania Pandian, Shivraj Savadkar, Ki Buom Lee, Alejandro Torres-Hernandez, Berk Aykut, Brian Diskin, Wei Wang, Mohammad S Farooq, Arif I Mahmud, Gregor Werba, Eduardo J Morales, Sarah Lall, Benjamin J Wadowski, Amanda G Rubin, Matthew E Berman, Rajkishen Narayanan, Mautin Hundeyin, George Miller
The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4(+) T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8(+) T cell activation...
April 25, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28442414/inhibition-of-allogeneic-cytotoxic-t-cell-cd8-proliferation-via-polymer-induced-treg-cd4-cells
#18
Ning Kang, Wendy M Toyofuku, Xining Yang, Mark D Scott
T cell-mediated immune rejection remains a barrier to successful transplantation. Polymer-based bioengineering of cells may provide an effective means of preventing allorecognition and the proliferation of cytotoxic (CD8(+)) T lymphocytes (CTL). Using MHC-disparate murine splenocytes modified with succinimidyl valerate activated methoxypoly(ethylene glycol) [SVA-mPEG] polymers, the effects of leukocyte immunocamouflage on CD8(+) and CD4(+) alloproliferation and T regulatory (Treg) cell induction were assessed in a mixed lymphocyte reaction (MLR) model...
April 23, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28439271/cross-talk-between-inhibitory-immunoreceptor-tyrosine-based-activation-motif-signaling-and-toll-like-receptor-pathways-in-macrophages-and-dendritic-cells
#19
REVIEW
Ivan Hirsch, Vaclav Janovec, Ruzena Stranska, Nathalie Bendriss-Vermare
The innate immune cells sense microbial infection and self-ligands by pathogen recognition receptors (PRRs), such as toll-like receptors (TLRs) and regulatory receptors (RRs), associated with immunoreceptor tyrosine-based activation motif (ITAM). Rapid activation and concerted action of PRRs signaling and feedback inhibitory mechanisms must be engaged to ensure the host defense functions and to prevent cytotoxicity associated with excessive activation. ITAM-associated RRs can generate stimulatory or, paradoxically, inhibitory signals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28432285/nod1-modulates-il-10-signalling-in-human-dendritic-cells
#20
Theresa Neuper, Kornelia Ellwanger, Harald Schwarz, Thomas A Kufer, Albert Duschl, Jutta Horejs-Hoeck
NOD1 belongs to the family of NOD-like receptors, which is a group of well-characterised, cytosolic pattern-recognition receptors. The best-studied function of NOD-like receptors is their role in generating immediate pro-inflammatory and antimicrobial responses by detecting specific bacterial peptidoglycans or by responding to cellular stress and danger-associated molecules. The present study describes a regulatory, peptidoglycan-independent function of NOD1 in anti-inflammatory immune responses. We report that, in human dendritic cells, NOD1 balances IL-10-induced STAT1 and STAT3 activation by a SOCS2-dependent mechanism, thereby suppressing the tolerogenic dendritic cell phenotype...
April 21, 2017: Scientific Reports
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