| 1. |
- Los, Marek Jan, et al.
(författare)
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Caspases : more than just killers?
- 2001
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Ingår i: Trends in immunology. - : Elsevier. - 1471-4906 .- 1471-4981. ; 22:1, s. 31-34
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Forskningsöversikt (refereegranskat)abstract
- Proteases of the caspase family constitute the central executioners of apoptosis, Several recent observations suggest that caspases and apoptosis-regulatory molecules exert important functions beyond that of cell death, including the control of T-cell proliferation and cell-cycle progression. Here, Los and colleagues propose a model that directly connects cell suicide mechanisms to the regulation of cell-cycle progression.
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| 2. |
- Abeler-Dörner, Lucie, et al.
(författare)
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Butyrophilins: an emerging family of immune regulators
- 2012
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4906 .- 1471-4981. ; 33:1, s. 34-41
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Forskningsöversikt (refereegranskat)abstract
- Butyrophilins (Btns) and butyrophilin-like (Btnl) molecules are emerging as novel regulators of immune responses in mice and humans. Several clues point to their probable importance: many of the genes are located within the MHC; they are structurally related to B7-co-stimulatory molecules; they are functionally implicated in T cell inhibition and in the modulation of epithelial cell-T cell interactions; and they are genetically associated with inflammatory diseases. Nonetheless, initial immersion into the current literature can uncover confusion over even basic information such as gene names and expression patterns, and seemingly conflicting data regarding the biological activities of different family members. This review addresses each of these issues, concluding with the attractive potential of Btn and Btnl molecules to act as specific attenuators of tissue-associated inflammatory responses.
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| 3. |
- Agace, William, et al.
(författare)
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How vitamin A metabolizing dendritic cells are generated in the gut mucosa.
- 2012
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Ingår i: Trends in Immunology. - : Elsevier BV. - 1471-4981 .- 1471-4906. ; 33, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- CD103(+) dendritic cells (DCs) represent the major migratory DC population in the intestinal lamina propria and are believed to play an essential role in the initiation and regulation of mucosal adaptive immune responses. Small intestine (SI) CD103(+) DCs have an enhanced capacity to generate the vitamin A metabolite, retinoic acid, a property that underlies their ability to induce the gut homing receptors CC chemokine receptor 9 and α4β7 on responding T and B cells, and enhance forkhead box P3(+) T regulatory and IgA plasma cell differentiation in vitro. In this review, we discuss the environmental signals that appear to promote vitamin A metabolising activity in SI CD103(+) DCs in the steady state and thus which may contribute to driving the unique nature of SI immune responses.
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| 4. |
- Agace, William
(författare)
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T-cell recruitment to the intestinal mucosa.
- 2008
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Ingår i: Trends in Immunology. - : Elsevier BV. - 1471-4981 .- 1471-4906. ; Oct 4., s. 514-522
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Tidskriftsartikel (refereegranskat)abstract
- The intestinal epithelium and underlying lamina propria contains large numbers of T cells that play an important role in maintaining intestinal homeostasis and defense against intestinal pathogens. Recent years have seen several significant advances in our understanding of the mechanisms regulating T-cell localization to the intestinal mucosa. For instance, we now know that the small intestine 'imprints' gut homing properties on T cells by inducing the expression of specific integrins and chemokine receptors. Further studies have identified distinct subsets of intestinal dendritic cells that use retinoic acid to generate both gut-tropic and regulatory T cells. As our understanding of the mechanisms regulating the generation of gut tropic T-cell populations evolves, the possibility of targeting these processes for mucosal vaccine development and treatment of intestinal immune pathology become more apparent.
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| 5. |
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| 6. |
- Borregaard, Niels, et al.
(författare)
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Neutrophil granules: a library of innate immunity proteins
- 2007
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Ingår i: Trends in Immunology. - : Elsevier BV. - 1471-4981 .- 1471-4906. ; 28:8, s. 340-345
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Forskningsöversikt (refereegranskat)abstract
- Gene expression profiling has revealed that circulating neutrophils rest between two major bursts of transcriptional and protein synthetic activities. The first occurs in the bone marrow. This equips the neutrophil with stocks of innate defense armory that are packaged into different granule subsets. The second burst occurs when the neutrophil exits circulation and migrates into tissues to find, capture and phagocytose microorganisms. This burst results in the synthesis and secretion of cytokines and chemokines that support resolution of inflammation and healing of damaged tissue. Gene expression profiling has revealed that neutrophils express a variety of innate immunity proteins, known previously only to be expressed in other cells. Likewise, it has become clear that some proteins previously thought to be specific to the neutrophil are expressed in epithelial cells during inflammation.
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| 7. |
- Bulfone-Paus, Silvia, et al.
(författare)
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Positive and Negative Signals in Mast Cell Activation
- 2017
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4906 .- 1471-4981. ; 38:9, s. 657-667
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Forskningsöversikt (refereegranskat)abstract
- Mast cells are powerful immune modulators of the tissue microenvironment. Within seconds of activation, these cells release a variety of preformed biologically active products, followed by a wave of mediator synthesis and secretion. Increasing evidence suggests that an intricate network of inhibitory and activating receptors, specific signaling pathways, and adaptor proteins governs mast cell responsiveness to stimuli. Here, we discuss the biological and clinical relevance of negative and positive signaling modalities that control mast cell activation, with an emphasis on novel Fc epsilon RI regulators, immunoglobulin E (IgE)-independent pathways [e.g., Mas-related G protein-coupled receptor X2 (MRGPRX2)], tetraspanins, and the CD300 family of inhibitory and activating receptors.
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| 8. |
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| 9. |
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| 10. |
- Cerenius, Lage, et al.
(författare)
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The proPO-system : pros and cons for its role in invertebrate immunity
- 2008
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4906 .- 1471-4981. ; 29:6, s. 263-271
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Forskningsöversikt (refereegranskat)abstract
- Melanisation is an important immune response in many invertebrates. Recent evidence also strongly implies that the melanisation (prophenoloxidase activating) cascade is intimately associated with the appearance of factors stimulating cellular defence by aiding phagocytosis and encapsulation reactions. However, some controversy exists in the field, and at least in flies and mosquitoes, the successful combat of some pathogens does not seem to be dependent on phenoloxidase activity. This may be because of redundancy among separate immune mechanisms, inappropriate testing, species differences or a combination thereof. Recently, by using RNA interference against phenoloxidase or in specific host-pathogen interactions where the pathogen prevents melanin production by the host, convincing data have confirmed the importance of this cascade in invertebrate innate immunity.
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| 11. |
- Christoffersson, Gustaf, et al.
(författare)
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Regulatory Immune Mechanisms beyond Regulatory T Cells
- 2019
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4906 .- 1471-4981. ; 40:6, s. 482-491
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Forskningsöversikt (refereegranskat)abstract
- In autoimmunity, aggressive immune responses are counteracted by suppressive rejoinders. For instance, FOXP3-expressing regulatory T cells (Tregs), have shown remarkable effects in limiting autoimmunity in preclinical models. However, early results from human Treg trials have not been as positive. Here, we highlight questions surrounding Treg transfers as putative treatments for autoimmunity. We discuss whether lack of antigenic recognition might be key to shifting cells from contributing to an aggressive autoresponse, to being part of a regulatory network. Moreover, we argue that identifying the physiological range of immunosuppression of Tregs might help potentiate their efficacy. We propose widening the view on immunoregulation by considering the participation of CD8(+) Tregs in this process, which could have major implications in autoimmunity.
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| 12. |
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| 13. |
- Esser, C, et al.
(författare)
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The aryl hydrocarbon receptor in immunity
- 2009
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4981 .- 1471-4906. ; 30:9, s. 447-454
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Tidskriftsartikel (refereegranskat)
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| 14. |
- Exley, Christopher, et al.
(författare)
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The immunobiology of aluminium adjuvants : how do they really work?
- 2010
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4906 .- 1471-4981. ; 31:3, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- Aluminium adjuvants potentiate the immune response, thereby ensuring the potency and efficacy of typically sparingly available antigen. Their concomitant critical importance in mass vaccination programmes may have prompted recent intense interest in understanding how they work and their safety. Progress in these areas is stymied, however, by a lack of accessible knowledge pertaining to the bioinorganic chemistry of aluminium adjuvants, and, consequently, the inappropriate application and interpretation of experimental models of their mode of action. The objective herein is, therefore, to identify the many ways that aluminium chemistry contributes to the wide and versatile armoury of its adjuvants, such that future research might be guided towards a fuller understanding of their role in human vaccinations.
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| 15. |
- Gerlach, C
(författare)
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Carmen Gerlach
- 2018
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4981 .- 1471-4906. ; 39:3, s. 167-170
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 16. |
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| 17. |
- Hultqvist, Malin, et al.
(författare)
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The protective role of ROS in autoimmune disease.
- 2009
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Ingår i: Trends in Immunology. - : Elsevier BV. - 1471-4981 .- 1471-4906. ; 30, s. 201-208
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Tidskriftsartikel (refereegranskat)abstract
- For a long time, reactive oxygen species (ROS) produced by the phagocyte NADPH oxidase (NOX2) complex have been considered harmful mediators of inflammation owing to their highly reactive nature. However, there are an increasing number of findings suggesting that ROS produced by the NOX2 complex are anti-inflammatory and prevent autoimmune responses, thus challenging existing dogma. ROS might not only be produced as a mechanism to eradicate invading pathogens, but rather as a means by which to fine-tune the inflammatory response, depending on when, where and at what amounts they are produced. In this review, we aim to describe the current findings highlighting ROS as regulators of autoimmune inflammation, focusing on autoimmune arthritis.
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| 18. |
- Kim, MS, et al.
(författare)
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The multiple roles of phosphoinositide 3-kinase in mast cell biology.
- 2008
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Ingår i: Trends in immunology. - 1471-4906 .- 1471-4981. ; 29:10, s. 493-501
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Forskningsöversikt (refereegranskat)abstract
- Mast cells play a central role in the initiation of inflammatory responses associated with asthma and other allergic disorders. Receptor-mediated mast cell growth, differentiation, homing to their target tissues, survival and activation are all controlled, to varying degrees, by phosphoinositide-3-kinase (PI3K)-driven pathways. It is not fully understood how such diverse responses can be differentially regulated by PI3K. However, recent studies have provided greater insight into the mechanisms that control, and those that are controlled by, different PI3K subunit isoforms in mast cells. In this review, we discuss how PI3K influences the mast cell processes described above. Furthermore, we describe how different mast cell receptors use alternative isoforms of PI3K for these functions and discuss potential downstream targets of these isoforms.
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| 19. |
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| 20. |
- Lernmark, A, et al.
(författare)
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Immunomodulation with human recombinant autoantigens
- 2005
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Ingår i: Trends in Immunology. - : Elsevier BV. - 1471-4981 .- 1471-4906. ; 26:11, s. 608-612
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Forskningsöversikt (refereegranskat)abstract
- The loss of beta cells in type 1 diabetes is the consequence of a T cell-dependent autoimmune attack. Autoantibodies against GAD65 (Mr 65.000 isoform of glutamic acid decarboxylase), IA-2 (insulinoma-associated protein IA-2) or insulin, alone or in combination, predict disease. Preclinical studies in spontaneously diabetic rodents suggest that immunomodulation with autoantigens might alter the course of autoimmune diabetes. Oral insulin reduces the development of diabetes in risk subjects with high insulin autoantibody levels. Giving alum-formulated GAD65 to patients classified with latent autoimmune diabetes of the adult (LADA) is safe and suggests possible immunomodulating effects of GAD65. Future immunomodulation trials might better ascertain subjects based on HLA genetic risk factors, the level of insulin that is still produced or by combining autoantigens with, for example, anti-CD3 antibodies, to induce antigen-specific tolerance and thereby a long-lasting protection for beta cells.
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| 21. |
- Markiewski, Maciej M., et al.
(författare)
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Complement and coagulation : strangers or partners in crime?
- 2007
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4906 .- 1471-4981. ; 28:4, s. 184-192
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Forskningsöversikt (refereegranskat)abstract
- The convergence between complement and the clotting system extends far beyond the chemical nature of the complement and coagulation components, both of which form proteolytic cascades. Complement effectors directly enhance coagulation. These effects are supplemented by the interactions of complement with other inflammatory mediators that can increase the thrombogenicity of blood. In addition, complement inhibits anticoagulant factors. The crosstalk between complement and coagulation is also well illustrated by the ability of certain coagulation enzymes to activate complement components. Understanding the interplay between complement and coagulation has fundamental clinical implications in the context of diseases with an inflammatory pathogenesis, in which complement-coagulation interactions contribute to the development of life-threatening complications. Here, we review the interactions of the complement system with hemostasis and their roles in various diseases.
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| 22. |
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| 23. |
- Muntjewerff, Elke M., et al.
(författare)
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Putative regulation of macrophage-mediated inflammation by catestatin
- 2022
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Ingår i: Trends in immunology. - : Elsevier. - 1471-4906 .- 1471-4981. ; 43:1, s. 41-50
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Forskningsöversikt (refereegranskat)abstract
- Catestatin (CST) is a bioactive cleavage product of the neuroendocrine prohormone chromogranin A (CgA). Recent findings show that CST can exert anti-inflammatory and antiadrenergic effects by suppressing the inflammatory actions of mammalian macrophages. However, recent findings also suggest that macrophages themselves are major CST producers. Here, we hypothesize that macrophages produce CST in an inflammation-dependent manner and thereby might self-regulate inflammation in an autocrine fashion. CST is associated with pathological conditions hallmarked by chronic inflammation, including autoimmune, cardiovascular, and metabolic disorders. Since intraperitoneal injection of CST in mouse models of diabetes and inflammatory bowel disease has been reported to be beneficial formitigating disease, we posit that CST should be further investigated as a candidate target for treating certain inflammatory diseases.
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| 24. |
- Nandakumar, Kutty Selva, 1965-, et al.
(författare)
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Therapeutic cleavage of IgG: new avenues for treating inflammation.
- 2008
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Ingår i: Trends in Immunology. - Cambridge, MA : Elsevier BV. - 1471-4981 .- 1471-4906. ; 29, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies developing in humans contribute to the pathogenesis of several diseases, and injected therapeutic antibodies can also trigger adverse side effects. An efficient and rapid elimination of these antibodies are therefore critically needed. Antibody removal by plasmapheresis and immunoadsorption are commonly used methods but have their own limitations. Bacterial enzymes that can cleave IgG molecules or remove carbohydrate moieties to ameliorate their immunogenicity or effector functions in vivo offer new avenues for drug development. Recent discoveries highlight the possibility of cleaving or modifying IgG in vivo by injection of enzymes. Such an approach opens up new therapeutic possibilities not only for the control of pathogenic antibody-mediated inflammatory diseases but also allograft rejection or the treatment of side-effects of 'biologicals' such as monoclonal antibodies.
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| 25. |
- Nilsson, Bo, et al.
(författare)
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Can cells and biomaterials in therapeutic medicine be shielded from innate immune recognition
- 2010
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4906 .- 1471-4981. ; 31:1, s. 32-38
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Tidskriftsartikel (refereegranskat)abstract
- Biomaterials (e.g. polymers, metals, or ceramics), cell and cell cluster (e.g. pancreatic islets) transplantation are beginning to offer novel treatment modalities for some otherwise intractable diseases. The innate immune system is involved in incompatibility reactions that occur when biomaterials or cells are introduced into the blood circulation. In particular, the complement, coagulation and contact systems are involved in the recognition of biomaterials and cells, eliciting activation of platelets and leukocytes. Such treatments are associated with anaphylactoid and thrombotic reactions, inflammation, and rejection of biomaterials and cells, leading to treatment failures and adverse reactions. We discuss here the new technologies that are being developed to shield the biomaterial and cell surfaces from recognition by the innate immune system.
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| 26. |
- Pawelec, Graham, et al.
(författare)
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Is immunosenescence infectious?
- 2004
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Ingår i: Trends in immunology. - 1471-4906 .- 1471-4981. ; 25:8, s. 406-410
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Tidskriftsartikel (refereegranskat)
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| 27. |
- Pejler, Gunnar, et al.
(författare)
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Novel insights into the biological function of mast cell carboxypeptidase A
- 2009
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4906 .- 1471-4981. ; 30:8, s. 401-408
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Forskningsöversikt (refereegranskat)abstract
- When mast cells are activated they can respond by releasing their secretory granule compounds, including mast cell-specific proteases of chymase, tryptase and carboxypeptidase A (MC-CPA) type. MC-CPA is a dominant protein component of the mast cell granule and the MC-CPA gene is extremely highly expressed. Despite this, relatively little has been known of its biological function. However, the recent generation of mouse strains lacking MC-CPA has opened up new possibilities for investigations related to this protease. This recent development has revealed a role for MC-CPA in regulating innate immunity responses, including the degradation of harmful substances such as the vasoconstrictive factor endothelin 1 and snake venom toxins. Here, we summarize the current knowledge of MC-CPA.
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| 28. |
- Phillipson, Mia, 1973-, et al.
(författare)
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The Healing Power of Neutrophils
- 2019
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Ingår i: Trends in immunology. - : Elsevier. - 1471-4906 .- 1471-4981. ; 40:7, s. 635-647
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Forskningsöversikt (refereegranskat)abstract
- Neutrophils promptly accumulate in large numbers at sites of tissue injury. Injuries to the skin or mucosae disrupt barriers against the external environment, and the bactericidal actions of neutrophils are important in preventing microbial invasion. Neutrophils have also been associated with exacerbated inflammation, for example in non-healing wounds or in conditions such as inflammatory bowel disease (IBD). However, additional neutrophil functions important for angiogenesis and tissue restoration have been uncovered in models of sterile and ischemic injury, as well as in tumors. These functions are also relevant in healing skin and mucosal wounds, and can be impaired in conditions associated with non-healing wounds, such as diabetes. Here, we discuss our current understanding of neutrophil contributions to healing, and how the latter can be compromised in disease.
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| 29. |
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| 30. |
- Sellin, Mikael E., et al.
(författare)
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Inflammasomes of the intestinal epithelium
- 2015
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4906 .- 1471-4981. ; 36:8, s. 442-450
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Tidskriftsartikel (refereegranskat)abstract
- While the functional importance of inflammasomes in blood-derived cell types is well established, it remains poorly understood how inflammasomes in nonhematopoietic cells contribute to mucosal immunity. Recent studies have revealed functional roles of inflammasomes - particularly NAIP/NLRC4, NLRP6, and noncanonical caspase-4 (caspase-11) - within epithelial cells of the gut in mucosal immune defense, inflammation, and tumorigenesis. Here, we review and discuss these findings in the broader context of tissue compartment-specific mucosal immunity. We propose several models whereby activities of the intestinal epithelial inflammasomes converge on mechanisms to remove compromised epithelial cells, maintain host-microbiota mutualism, and communicate with immune cells of the underlying lamina propria.
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| 31. |
- Sjoberg, A. P., et al.
(författare)
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Complement activation and inhibition: a delicate balance
- 2009
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Ingår i: Trends in Immunology. - : Elsevier BV. - 1471-4981 .- 1471-4906. ; 30:2, s. 83-90
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Forskningsöversikt (refereegranskat)abstract
- Complement is part of the innate immune defence and not only recognizes microbes but also unwanted host molecules to enhance phagocytosis and clearance. This process of opsonisation must be tightly regulated to prevent immunopathology. Endogenous ligands such as dying cells, extracellular matrix proteins, pentraxins, amyloid deposits, prions and DNA, all bind the complement activator C1q, but also interact with complement inhibitors Cob-binding protein and factor H. This contrasts to the interaction between C1q and immune complexes, in which case no inhibitors bind, resulting in full complement activation. Disturbances to the complement regulation on endogenous ligands can lead to diseases such as age-related macular degeneration, neurological and rheumatic disorders. A thorough understanding of these processes might be crucial to developing new therapeutic strategies.
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| 32. |
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| 33. |
- Soehnlein, O
(författare)
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Neutrophil Research, Quo Vadis?
- 2019
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Ingår i: Trends in immunology. - : Elsevier BV. - 1471-4981 .- 1471-4906. ; 40:7, s. 561-564
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Tidskriftsartikel (refereegranskat)
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Bemark, Mats, et al.
(författare)
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Gut-associated lymphoid tissue: a microbiota-driven hub of B cell immunity
- 2024
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Ingår i: Trends in Immunology. - 1471-4981. ; 45:3, s. 211-223
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Forskningsöversikt (refereegranskat)abstract
- The diverse gut microbiota, which is associated with mucosal health and general wellbeing, maintains gut-associated lymphoid tissues (GALT) in a chronically activated state, including sustainment of germinal centers in a context of high antigenic load. This influences the rules for B cell engagement with antigen and the potential consequences. Recent data have highlighted differences between GALT and other lymphoid tissues. For example, GALT propagates IgA responses against glycans that show signs of having been generated in germinal centers. Other findings suggest that humans are among those species where GALT supports the diversification, propagation, and possibly selection of systemic B cells. Here, we review novel findings that identify GALT as distinctive, and able to support these processes.
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| 48. |
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| 49. |
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| 50. |
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