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| 4. |
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| 5. |
- Cichocki, Frank, et al.
(författare)
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NK cell development and function - Plasticity and redundancy unleashed.
- 2014
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Ingår i: Seminars in Immunology. - : Elsevier BV. - 1096-3618 .- 1044-5323. ; 26:2, s. 114-126
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Forskningsöversikt (refereegranskat)abstract
- Bone marrow-derived natural killer (NK) cells constitute the major subset of cytotoxic lymphocytes in peripheral blood. They provide innate defense against intracellular infection or malignancy and contribute to immune homeostasis. Large numbers of NK cells are also present in tissues, including the liver and uterus, where they can mediate immunosurveillance but also play important roles in tissue remodeling and vascularization. Here, we review the pathways involved in NK cell lineage commitment and differentiation, discussing relationships to other lymphocyte populations and highlighting genetic determinants. Characterizing NK cells from distinct tissues and during infections have revealed subset specializations, reflecting inherent cellular plasticity. In this context, we discuss how different environmental and inflammatory stimuli may shape NK cells. Particular emphasis is placed on genes identified as being critical for NK cell development, differentiation, and function from studies of model organisms or associations with disease. Such studies are also revealing important cellular redundancies. Here, we provide a view of the genetic framework constraining NK cell development and function, pinpointing molecules required for these processes but also underscoring plasticity and redundancy that may underlie robust immunological function. With this view, built in redundancy may highlight the importance of NK cells to immunity.
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| 6. |
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| 7. |
- Ekdahl, Kristina N., et al.
(författare)
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Complement inhibition in biomaterial- and biosurface-induced thromboinflammation
- 2016
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Ingår i: Seminars in Immunology. - : Elsevier BV. - 1044-5323 .- 1096-3618. ; 28:3, s. 268-277
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic medicine today includes a vast number of procedures involving the use of biomaterials, transplantation of therapeutic cells or cell clusters, as well as of solid organs. These treatment modalities are obviously of great benefit to the patient, but also present a great challenge to the innate immune system, since they involve direct exposure of non-biological materials, cells of non-hematological origin as well as endothelial cells, damaged by ischemia-perfusion in solid organs to proteins and cells in the blood. The result of such an exposure may be an inappropriate activation of the complement and contact/kallikrein systems, which produce mediators capable of triggering the platelets and PMNs and monocytes, which can ultimately result in thrombotic and inflammatory (i.e., a thrombo-inflammatory) response to the treatment modality. In this concept review, we give an overview of the mechanisms of recognition within the innate immunity system, with the aim to identify suitable points for intervention. Finally, we discuss emerging and promising techniques for surface modification of biomaterials and cells with specific inhibitors in order to diminish thromboinflammation and improve clinical outcome.
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| 8. |
- Gerold, Gisa, 1979-, et al.
(författare)
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What is the role of Toll-like receptors in bacterial infections?
- 2007
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Ingår i: Seminars in Immunology. - : Elsevier BV. - 1044-5323 .- 1096-3618. ; 19:1, s. 41-7
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Tidskriftsartikel (refereegranskat)abstract
- Innate immunity relies on signalling by Toll-like receptors (TLRs) to alert the immune system of the presence of invading bacteria. TLR activation leads to the release of cytokines that allow for effective innate and adaptive immune responses. However, the contribution of different TLRs depends on the site of the infection and the pathogen. This review will describe the involvement of TLRs in the development of three different bacterial infections as well as our current understanding of the role of TLRs during microbial pathogenesis.
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| 9. |
- Gul, Ersin, et al.
(författare)
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Epithelial inflammasomes, gasdermins, and mucosal inflammation - Lessons from Salmonella and Shigella infected mice
- 2023
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Ingår i: Seminars in Immunology. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 1044-5323 .- 1096-3618. ; 70
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Forskningsöversikt (refereegranskat)abstract
- Besides its crucial function in nutrient absorbance and as barrier against the microbiota, the gut epithelium is essential for sensing pathogenic insults and mounting of an appropriate early immune response. In mice, the activation of the canonical NAIP/NLRC4 inflammasome is critical for the defense against enterobacterial infections. Activation of the NAIP/NLRC4 inflammasome triggers the extrusion of infected intestinal epithelial cells (IEC) into the gut lumen, concomitant with inflammasome-mediated lytic cell death. The membrane permeabilization, a hallmark of pyroptosis, is caused by the pore-forming proteins called gasdermins (GSDMs). Recent work has revealed that NAIP/NLRC4-dependent extrusion of infected IECs can, however, also be executed in the absence of GSDMD. In fact, several reports highlighted that various cell death pathways (e.g., pyroptosis or apoptosis) and unique mechanisms specific to particular infection models and stages of gut infection are in action during epithelial inflammasome defense against intestinal pathogens. Here, we summarize the current knowledge regarding the underlying mechanisms and speculate on the putative functions of the epithelial inflammasome activation and cell death, with a particular emphasis on mouse infection models for two prominent enterobacterial pathogens, Salmonella Typhimurium and Shigella flexneri.
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| 10. |
- Harandi, Ali M, 1968
(författare)
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Systems analysis of human vaccine adjuvants
- 2018
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Ingår i: Seminars in Immunology. - : Elsevier BV. - 1044-5323. ; 39:C (Special Issue: SI ), s. 30-34
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Tidskriftsartikel (refereegranskat)abstract
- The discovery and wide spread use of vaccines have saved millions of lives in the past few decades. Vaccine adjuvants represent an integral part of the modem vaccines. Despite numerous efforts, however, only a handful of vaccine adjuvants is currently available for human use. A comprehensive understanding of the mechanisms of action of adjuvants is pivotal to harness the potential of existing and new adjuvants in mounting desirable immune responses to counter human pathogens. Decomposing the host response to vaccines and its components at systems level has recently been made possible owing to the recent advancements in Omics technology and cutting edge immunological assays powered by systems biology approaches. This approach has begun to shed light on the molecular signatures of several human vaccines and adjuvants. This review is an attempt to provide an overview of the recent efforts in systems analysis of vaccine adjuvants that are currently in clinic.
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| 11. |
- Holmes, TD, et al.
(författare)
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Natural killer cell memory in context
- 2016
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Ingår i: Seminars in immunology. - : Elsevier BV. - 1096-3618 .- 1044-5323. ; 28:4, s. 368-376
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Tidskriftsartikel (refereegranskat)
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| 12. |
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| 13. |
- Le Pendu, Jacques, et al.
(författare)
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Mendelian resistance to human norovirus infections
- 2006
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Ingår i: Seminars in Immunology. - : Elsevier BV. - 1044-5323 .- 1096-3618. ; 18:6, s. 375-386
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Tidskriftsartikel (refereegranskat)abstract
- Noroviruses have emerged as a major cause of acute gastroenteritis in humans of all ages. Despite high infectivity of the virus and lack of long-term immunity, volunteer and authentic studies has suggested the existence of inherited protective factors. Recent studies have shown that histo-blood group antigens (HBGAs) and in particular secretor status controlled by the α1,2fucosyltransferase FUT2 gene determine susceptibility to norovirus infections, with nonsecretors (FUT2-/-), representing 20% of Europeans, being highly resistant to symptomatic infections with major strains of norovirus. Moreover, the capsid protein from distinct strains shows different HBGA specificities, suggesting a host-pathogen co-evolution driven by carbohydrate-protein interactions. © 2006.
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| 15. |
- Lokmic, Zerina, et al.
(författare)
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The extracellular matrix of the spleen as a potential organizer of immune cell compartments.
- 2008
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Ingår i: Seminars in immunology. - : Elsevier BV. - 1044-5323. ; 20:1, s. 4-13
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Forskningsöversikt (refereegranskat)abstract
- Until recently little information was available on the molecular details of the extracellular matrix (ECM) of secondary lymphoid tissues. There is now growing evidence that these ECMs are unique structures, combining characteristics of basement membranes and interstitial or fibrillar matrices, resulting in scaffolds that are strong and highly flexible and, in certain secondary lymphoid compartments, also forming conduit networks for rapid fluid transport. This review will address the structural characteristics of the ECM of the murine spleen and its potential role as an organizer of immune cell compartments, with reference to the lymph node where relevant.
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| 16. |
- Loskog, Angelica, et al.
(författare)
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The Janus faces of CD40 in cancer
- 2009
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Ingår i: Seminars in Immunology. - : Elsevier BV. - 1044-5323 .- 1096-3618. ; 21:5, s. 301-307
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Forskningsöversikt (refereegranskat)abstract
- CD40 is a TNF receptor family member that is widely recognized for its prominent role in immune regulation and homeostasis. Expression of CD40 is not restricted to normal lymphoid cells but is also evident in the majority of haemopoietic and epithelial malignancies where it has been implicated in oncogenic events. Accumulating evidence, however, suggests that the CD40 pathway can be exploited for cancer therapy by virtue of its ability to stimulate the host anti-tumor immune response, normalize the tumor microenvironment and directly suppress the growth of CD40-positive tumors. Here, we provide an overview of the multifaceted functions of the CD40 pathway in cancer and its emerging role in the treatment of malignancy.
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| 17. |
- Luc, Sidinh, et al.
(författare)
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Delineating the cellular pathways of hematopoietic lineage commitment.
- 2008
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Ingår i: Seminars in Immunology. - : Elsevier BV. - 1096-3618 .- 1044-5323. ; 20, s. 213-220
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Tidskriftsartikel (refereegranskat)abstract
- The prevailing model for adult hematopoiesis postulates that the first lineage commitment step results in a strict separation of common myeloid and common lymphoid pathways. However, the recent identification of granulocyte/monocyte (GM)-lymphoid restricted lymphoid-primed multipotent progenitors (LMPPs) and primitive common myeloid progenitors (CMPs) within the "HSC" compartment provide compelling support for establishment of independent GM-megakaryocyte/erythroid (GM-MkE) and GM-lymphoid commitment pathways as decisive early lineage fate decisions. These changes in lineage potentials are corroborated by corresponding changes in multilineage transcriptional priming, as LMPPs down-regulate MkE priming but become GM-lymphoid transcriptionally primed, whereas CMPs are GM-MkE primed. These distinct biological and molecular relationships are established already in the fetal liver.
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| 18. |
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| 19. |
- Mannes, Marco, et al.
(författare)
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Complement C3 activation in the ICU : Disease and therapy as Bonnie and Clyde
- 2022
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Ingår i: Seminars in Immunology. - : Elsevier. - 1044-5323 .- 1096-3618. ; 60
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Forskningsöversikt (refereegranskat)abstract
- Patients in the intensive care unit (ICU) often straddle the divide between life and death. Understanding the complex underlying pathomechanisms relevant to such situations may help intensivists select broadly acting treatment options that can improve the outcome for these patients. As one of the most important defense mechanisms of the innate immune system, the complement system plays a crucial role in a diverse spectrum of diseases that can necessitate ICU admission. Among others, myocardial infarction, acute lung injury/acute respiratory distress syndrome (ARDS), organ failure, and sepsis are characterized by an inadequate complement response, which can potentially be addressed via promising intervention options. Often, ICU monitoring and existing treatment options rely on massive intervention strategies to maintain the function of vital organs, and these approaches can further contribute to an unbalanced complement response. Artificial surfaces of extracorporeal organ support devices, transfusion of blood products, and the application of anticoagulants can all trigger or amplify undesired complement activation. It is, therefore, worth pursuing the evaluation of complement inhibition strategies in the setting of ICU treatment. Recently, clinical studies in COVID-19-related ARDS have shown promising effects of central inhibition at the level of C3 and paved the way for prospective investigation of this approach. In this review, we highlight the fundamental and often neglected role of complement in the ICU, with a special focus on targeted complement inhibition. We will also consider complement substitution therapies to temporarily counteract a disease/treatment-related complement consumption.
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| 20. |
- Mollnes, Tom E., et al.
(författare)
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Application of the C3 inhibitor compstatin in a human whole blood model designed for complement research-20 years of experience and future perspectives
- 2022
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Ingår i: Seminars in Immunology. - : Elsevier. - 1044-5323 .- 1096-3618. ; 59
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Forskningsöversikt (refereegranskat)abstract
- The complex molecular and cellular biological systems that maintain host homeostasis undergo continuous crosstalk. Complement, a component of innate immunity, is one such system. Initially regarded as a system to protect the host from infection, complement has more recently been shown to have numerous other functions, including involvement in embryonic development, tissue modeling, and repair. Furthermore, the complement system plays a major role in the pathophysiology of many diseases. Through interactions with other plasma cascades, including hemostasis, complement activation leads to the broad host-protective response known as thromboinflammation. Most complement research has been limited to reductionistic models of purified components and cells and their interactions in vitro. However, to study the pathophysiology of complement-driven diseases, including the interaction between the complement system and other inflammatory systems, holistic models demonstrating only minimal interference with complement activity are needed. Here we describe two such models; whole blood anticoagulated with either the thrombin inhibitor lepirudin or the fibrin polymerization peptide blocker GPRP, both of which retain complement activity and preserve the ability of complement to be mutually reactive with other inflammatory systems. For instance, to examine the relative roles of C3 and C5 in complement activation, it is possible to compare the effects of the C3 inhibitor compstatin effects to those of inhibitors of C5 and C5aR1. We also discuss how complement is activated by both pathogen-associated molecular patterns, inducing infectious inflammation caused by organisms such as Gram-negative and Gram-positive bacteria, and by sterile damage-associated molecular patterns, including cholesterol crystals and artificial materials used in clinical medicine. When C3 is inhibited, it is important to determine the mechanism by which inflammation is attenuated, i.e., whether the attenuation derives directly from C3 activation products or via downstream activation of C5, since the mechanism involved may determine the appropriate choice of inhibitor under various conditions. With some exceptions, most inflammatory responses are dependent on C5 and C5aR1; one exception is venous air embolism, in which air bubbles enter the blood circulation and trigger a mainly C3-dependent thromboembolism, with the formation of an active C3 convertase, without a corresponding C5 activation. Under such conditions, an inhibitor of C3 is needed to attenuate the inflammation. Our holistic blood models will be useful for further studies of the inhibition of any complement target, not just C3 or C5. The focus here will be on targeting the critical complement component, activation product, or receptor that is important for the pathophysiology in a variety of disease conditions.
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| 22. |
- Niessl, J, et al.
(författare)
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T cell immunity to SARS-CoV-2
- 2021
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Ingår i: Seminars in immunology. - : Elsevier BV. - 1096-3618 .- 1044-5323. ; 55, s. 101505-
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Tidskriftsartikel (refereegranskat)
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| 24. |
- Rönnblom, Lars, et al.
(författare)
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The type I interferon system in the development of lupus
- 2011
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Ingår i: Seminars in Immunology. - : Elsevier BV. - 1044-5323 .- 1096-3618. ; 23:2, s. 113-121
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Forskningsöversikt (refereegranskat)abstract
- The type I interferon (IFN) system induces inhibition of viral replication, but can also activate the innate and adaptive immune system. An important role of the type I IFN system in autoimmune diseases, including lupus, is suggested by the observation that these disorders display a prominent over-expression of type I IFN regulated genes. The development of autoimmune diseases in some individuals treated with IFN-α directly supports a pivotal role for this cytokine in breaking tolerance and inducing autoimmune reactions. A genetic setup that promotes type I IFN production and/or response and the presence of endogenous inducers of IFN-α production have been described in patients with lupus. Several known environmental risk factors for development of lupus or disease flares may contribute to the ongoing type I IFN production. In the present review we will describe the possible role of the type I IFN system in the lupus disease process. The possible connection between the type I IFN system and some environmental and genetic risk factors for lupus is also discussed.
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| 27. |
- Wan, M, et al.
(författare)
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Biosynthesis of leukotriene B4
- 2017
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Ingår i: Seminars in immunology. - : Elsevier BV. - 1096-3618 .- 1044-5323. ; 33:C, s. 3-15
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Tidskriftsartikel (refereegranskat)
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| 28. |
- Welinder, Eva, et al.
(författare)
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B-lymphocyte commitment : Identifying the point of no return
- 2011
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Ingår i: Seminars in Immunology. - : Elsevier. - 1044-5323 .- 1096-3618. ; 23:5, s. 335-340
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Forskningsöversikt (refereegranskat)abstract
- Even though B-lymphocyte development is one of the best understood models for cell differentiation in the hematopoetic system, recent advances in cell sorting and functional genomics has increased this understanding further. This has suggested that already early lymphoid primed multipotent progenitor cells (LMPPs) express low levels of lymphoid restricted transcripts. The expression of these genes becomes more pronounced when cells enter the FLT-3/IL-7 receptor positive common lymphoid progenitor (CLP) stage. However, the expression of B-lineage specific genes is limited to a B-cell restricted Ly6D surface positive subpopulation of the CLP compartment. The gene expression patterns also reflect differences in lineage potential and while Ly6D negative FLT-3/IL-7 receptor positive cells represents true CLPs with an ability to generate B/T and NK cells, the Ly6D positive cells lack NK cell potential and display a reduced T-cell potential in vivo. These recent findings suggest that the CLP compartment is highly heterogenous and that the point of no return in B-cell development may occur already in B220(-) CD19(-) cells. These findings have allowed for a better understanding of the interplay between transcription factors like EBF-1, PAX-5 and E47, all known as crucial for normal B-cell development. In this review, we aim to provide a comprehensive overview of B-cell fate specification and commitment based on the recent advances in the understanding of molecular networks as well as functional properties of early progenitor populations. (C) 2011 Elsevier Ltd. All rights reserved.
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