scholarly journals Inflammatory arthritis can be reined in by CpG-induced DC–NK cell cross talk

2007 ◽  
Vol 204 (8) ◽  
pp. 1911-1922 ◽  
Author(s):  
Hsin-Jung Wu ◽  
Heloisa Sawaya ◽  
Bryce Binstadt ◽  
Margot Brickelmaier ◽  
Amanda Blasius ◽  
...  
Keyword(s):  
Immune System ◽  
Cross Talk ◽  
Inflammatory Arthritis ◽  
Nk Cell ◽  
Therapeutic Potential ◽  
Adaptive Immune System ◽  
Interleukin 12 ◽  
Inhibitory Influence ◽  
Cpg Oligodeoxynucleotides ◽  
Cpg Odns

Unmethylated CpG-oligodeoxynucleotides (ODNs) are generally thought of as potent adjuvants with considerable therapeutic potential to enhance immune responses against microbes and tumors. Surprisingly, certain so-called stimulatory CpG-ODNs strongly inhibited the effector phase of inflammatory arthritis in the K/BxN serum transfer system, either preventively or therapeutically. Also unexpected was that the inhibitory influence did not depend on the adaptive immune system cells mobilized in an immunostimulatory context. Instead, they relied on cells of the innate immune system, specifically on cross talk between CD8α+ dendritic cells and natural killer cells, resulting in suppression of neutrophil recruitment to the joint, orchestrated through interleukin-12 and interferon-γ. These findings highlight potential applications of CpG-ODNs and downstream molecules as antiinflammatory agents.

Natural Products: Experimental Efficient Agents for Inflammatory Bowel Disease Therapy

2020 ◽  
Vol 25 (46) ◽  
pp. 4893-4913 ◽  
Author(s):  
Fan Cao ◽  
Jie Liu ◽  
Bing-Xian Sha ◽  
Hai-Feng Pan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Natural Products ◽  
Immune System ◽  
Bowel Disease ◽  
Therapeutic Potential ◽  
Adaptive Immune System ◽  
Receptor Protein ◽  
Intestinal Epithelia ◽  
Inflammatory Bowel ◽  
The Individual

: Inflammatory bowel disease (IBD) is a chronic, elusive disorder resulting in relapsing inflammation of intestine with incompletely elucidated etiology, whose two representative forms are ulcerative colitis (UC) and Crohn’s disease (CD). Accumulating researches have revealed that the individual genetic susceptibility, environmental risk elements, intestinal microbial flora, as well as innate and adaptive immune system are implicated in the pathogenesis and development of IBD. Despite remarkable progression of IBD therapy has been achieved by chemical drugs and biological therapies such as aminosalicylates, corticosteroids, antibiotics, anti-tumor necrosis factor (TNF)-α, anti-integrin agents, etc., healing outcome still cannot be obtained, along with inevitable side effects. Consequently, a variety of researches have focused on exploring new therapies, and found that natural products (NPs) isolated from herbs or plants may serve as promising therapeutic agents for IBD through antiinflammatory, anti-oxidant, anti-fibrotic and anti-apoptotic effects, which implicates the modulation on nucleotide- binding domain (NOD) like receptor protein (NLRP) 3 inflammasome, gut microbiota, intestinal microvascular endothelial cells, intestinal epithelia, immune system, etc. In the present review, we will summarize the research development of IBD pathogenesis and current mainstream therapy, as well as the therapeutic potential and intrinsic mechanisms of NPs in IBD.

Abstract TP79: Inhibition of Toll Like Receptor-4 (tlr4) Improves Neurobehavioral Outcomes After Acute Ischemic Stroke in Diabetic Rats

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yasir Abdul ◽  
Mohammed Abdelsaid ◽  
Wieguo Li ◽  
Guangkuo Dong ◽  
Adviye Ergul
Keyword(s):  
Ischemic Stroke ◽  
Immune System ◽  
Functional Outcomes ◽  
Therapeutic Potential ◽  
Adaptive Immune System ◽  
Artery Occlusion ◽  
Stroke Recovery ◽  
Microvascular Endothelial Cell ◽  
Poor Recovery ◽  
Tlr4 Receptor

Introduction: Diabetes increases the risk of occurrence and poor recovery of ischemic stroke injury. Activation of adaptive immune system and resulting inflammation contributes to neurovascular injury and deterioration of neurological functions post stroke in diabetes. We have shown that activation of TLR4, a key player in the innate immune system, decreases brain microvascular endothelial cell survival after hypoxic injury in diabetic conditions. Our previous work also demonstrated greater bleeding/edema and poor recovery after stroke in diabetes. Current study tested the hypothesis that activation of TLR4 contributes to worsened stroke injury in diabetes and its inhibition can improve functional outcomes. Methods: Low dose of Streptozotocin (30mg/kg) and high fat diet were used to induce type 2 diabetes in male Wistar rats. Middle cerebral artery occlusion for 60 mins was performed in 13 weeks old animals. Expression of TLR4 receptor in brain homogenates and cerebral microvasculature were assessed by immunoblotting (relative density). Another set of animals was treated with TLR4 inhibitor TAK242 (3mg/kg; i.p. after reperfusion, 24 and 48 hours). Neurobehavioral deficits were measured by composite score and adhesive removal test at baseline, day 1 and 3 post ischemic stroke. Results: Ischemic stroke increased the expression of TLR4 receptor in ischemic hemisphere (0.50±0.06 sham, 0.68±0.02 control and 1.24±2.0* diabetic; *p<0.05 vs sham) as well as in microvasculature (0.55±035 sham, 1.34±0.24 control and 9.49±2.5* diabetic; *p<0.05 vs sham) and this was significantly higher in diabetic animals. Diabetes worsened functional outcomes and inhibition of TLR4 significantly improved the deficits (Table). Conclusions: Our findings that TLR4 is highly upregulated in the microvasculature and that beneficial effects of TLR4 inhibition are more profound in diabetes suggest that vascular TLR4 holds a therapeutic potential for stroke recovery in diabetes.

The activation of the adaptive immune system: Cross-talk between antigen-presenting cells, T cells and B cells

2014 ◽  
Vol 162 (2) ◽  
pp. 103-112 ◽  
Author(s):  
Joke M.M. den Haan ◽  
Ramon Arens ◽  
Menno C. van Zelm
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Cross Talk ◽  
Adaptive Immune System ◽  
Antigen Presenting Cells ◽  
Adaptive Immune ◽  
Antigen Presenting

scholarly journals CRISPR as a Versatile Technology for Gene Activation and Genome Editing

2018 ◽  
Vol 4 ◽  
pp. 5
Author(s):  
Habib Rezanejadbardeji ◽  
Bahareh Behroozi-Asl ◽  
Raheleh Amirkhah
Keyword(s):  
Immune System ◽  
Therapeutic Potential ◽  
Genetic Disorders ◽  
Gene Activation ◽  
Adaptive Immune System ◽  
Stem Cell Differentiation ◽  
Zinc Finger Nucleases ◽  
Viral Gene ◽  
Transcription Activator ◽  
Adaptive Immune

CRISPR/Cas system, a microbial adaptive immune system, has rapidly transformed the ways researchers can interrogate the genome. CRISPR has many advantages over traditional methods such as Transcription activator-like effector nucleases (TALEN) and Zinc-finger nucleases (ZFN). Since CRISPR discovery as an adaptive immune system used by bacterial against viruses, it has been repurposed to help in many different genome-related studies such as gene knocking in and out, gene expression upregulation and downregulation. Also CRISPR holds vast therapeutic potential for the management of genetic disorders by straight modifying disease-causing mutations. Although the Cas9 protein has been revealed to attach and cleave DNA at off-target sites, the field of Cas9 specificity is quickly progressing, with marked modifying in guide RNA choice, protein and guide engineering, innovative enzymes, and off-target recognition methods. In current review we mostly focus on CRISPR unique ability in gene activation/ upregulation, which has wide applications in different aspects such as gene studies, stem cell differentiation, and trans-differentiation. Compared to other gene activation methods such as viral gene overexpression, TALEN and ZFN, CRISPR offers many benefits such as easy designing and high precision.

scholarly journals Immunomodulatory Effects of CpG Oligodeoxynucleotides on Established Th2 Responses

2002 ◽  
Vol 9 (6) ◽  
pp. 1260-1269 ◽  
Author(s):  
Kunihiko Kitagaki ◽  
Vipul V. Jain ◽  
Thomas R. Businga ◽  
Iftikhar Hussain ◽  
Joel N. Kline
Keyword(s):  
Allergic Diseases ◽  
Interleukin 12 ◽  
Dependent Manner ◽  
Independent Manner ◽  
Concentration Dependent Manner ◽  
Cpg Oligodeoxynucleotides ◽  
Th2 Responses ◽  
Cpg Odns ◽  
Ifn Γ

ABSTRACT CpG oligodeoxynucleotides (CpG ODNs) are known to induce type 1 T-helper-cell (Th1) responses. We have previously demonstrated that CpG ODNs administered during sensitization prevent Th2-mediated eosinophilic airway inflammation in vivo. We also reported that key Th1 cytokines, gamma interferon (IFN-γ) and interleukin 12 (IL-12), are not necessary for this protection. Recent in vivo data suggest that CpG ODNs might also reverse established pulmonary eosinophilia. In order to clarify how CpG ODNs can inhibit established Th2 responses, we evaluated the cytokine production from splenocytes from antigen- and alum-immunized mice. Restimulation with antigen induced IL-5, which was clearly inhibited by coculture with CpG ODNs in a concentration-dependent manner. CpG ODNs also induced IFN-γ, but in a concentration-independent manner. The inhibition of IL-5 production was not mediated through natural killer cells or via CD8+ T lymphocytes. Although IFN-γ plays an important role in inhibition of antigen-induced IL-5 production by CpG ODNs, IFN-γ was not the sole factor in IL-5 inhibition. CpG ODNs also induced IL-10, and this induction correlated well with IL-5 inhibition. Elimination of IL-10 reduced the anti-IL-5 effect of CpG ODNs, although incompletely. This may be because IFN-γ, induced by CpG ODNs, is also inhibited by IL-10, serving as a homeostatic mechanism for the Th1-Th2 balance. Overproduction of IFN-γ was downregulated by CpG ODN-induced IL-10 via modulation of IL-12 production. These data suggest that CpG ODNs may inhibit established Th2 immune responses through IFN-γ and IL-10 production, the latter serving to regulate excessive Th1 bias. These properties of CpG ODNs might be a useful feature in the development of immunotherapy adjuvants against allergic diseases such as asthma.

scholarly journals The Vicious Cross-Talk between Tumor Cells with an EMT Phenotype and Cells of the Immune System

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 460 ◽  
Author(s):  
Elisabetta Romeo ◽  
Carmelo Antonio Caserta ◽  
Cristiano Rumio ◽  
Fabrizio Marcucci
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
Cross Talk ◽  
Immune Cells ◽  
Epithelial Mesenchymal Transition ◽  
Large Body ◽  
Adaptive Immune System ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Immune Exclusion

Carcinoma cells that undergo an epithelial-mesenchymal transition (EMT) and display a predominantly mesenchymal phenotype (hereafter EMT tumor cells) are associated with immune exclusion and immune deviation in the tumor microenvironment (TME). A large body of evidence has shown that EMT tumor cells and immune cells can reciprocally influence each other, with EMT cells promoting immune exclusion and deviation and immune cells promoting, under certain circumstances, the induction of EMT in tumor cells. This cross-talk between EMT tumor cells and immune cells can occur both between EMT tumor cells and cells of either the native or adaptive immune system. In this article, we review this evidence and the functional consequences of it. We also discuss some recent evidence showing that tumor cells and cells of the immune system respond to similar stimuli, activate the expression of partially overlapping gene sets, and acquire, at least in part, identical functionalities such as migration and invasion. The possible significance of these symmetrical changes in the cross-talk between EMT tumor cells and immune cells is addressed. Eventually, we also discuss possible therapeutic opportunities that may derive from disrupting this cross-talk.

scholarly journals Generation of Natural Killer Cell Memory during Viral Infection

2015 ◽  
Vol 7 (6) ◽  
pp. 557-562 ◽  
Author(s):  
Timothy E. O'Sullivan ◽  
Joseph C. Sun
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Adaptive Immune System ◽  
Current Evidence ◽  
Cell Memory ◽  
Independent Manner ◽  
Adaptive Immune

Immunological memory is classically regarded as an attribute of antigen-specific T and B lymphocytes of the adaptive immune system. Cells of the innate immune system, including natural killer (NK) cells, have been considered short-lived cytolytic cells that can rapidly respond against pathogens in an antigen-independent manner and then die off. However, NK cells have recently been described to possess traits of adaptive immunity, such as clonal expansion after viral antigen exposure to generate long-lived memory cells. In this review, we will discuss the current evidence for viral-induced NK cell memory in both mice and humans.

scholarly journals NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency

2021 ◽  
Author(s):  
Dominic Lenz ◽  
Jens Pahl ◽  
Fabian Hauck ◽  
Seham Alameer ◽  
Meena Balasubramanian ◽  
...  
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Cell Activation ◽  
Nk Cell ◽  
Adaptive Immune System ◽  
Target Cells ◽  
Multisystem Disorder ◽  
Adaptive Immune ◽  
B Cell Deficiency

Abstract Purpose Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. Methods Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. Results Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell–intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia. Conclusion In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity.

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