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- Holmdahl, Rikard, et al.
(författare)
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Arthritis induced in rats with non-immunogenic adjuvants as models for rheumatoid arthritis
- 2001
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Ingår i: Immunological Reviews. - : Wiley. - 1600-065X .- 0105-2896. ; 184
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Forskningsöversikt (refereegranskat)abstract
- Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of alphabetaTCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans.
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| 2. |
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| 3. |
- Zandi, Sasan, et al.
(författare)
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Load and lock: the molecular mechanisms of B-lymphocyte commitment
- 2010
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Ingår i: IMMUNOLOGICAL REVIEWS. - : Blackwell Publishing Ltd. - 0105-2896. ; 238:1, s. 47-62
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Forskningsöversikt (refereegranskat)abstract
- The maturation of B-lymphoid cells from hematopoietic stem cells in the bone marrow is a complex process under control of interplay between extrinsic and intrinsic factors. In addition to serving as a model for normal cell differentiation, disturbances in this process results in immunodeficiencies and malignancies, such as leukemia and lymphoma, making the subject of high relevance for modern medicine. Although the process of B lymphopoiesis has been under intense investigation, recent methodological developments within the area of cell sorting, genome-wide expression, and DNA-binding analysis has allowed for a rapid development of the understanding of B-lymphocyte differentiation. This has suggested that the path to B-lymphoid cell fate may be initiated by lineage priming reflected in the expression of lymphoid associated genes already in multipotent hematopoietic progenitors. Upon differentiation, the gene expression profile is changed to involve an increasing number of B-lineage-restricted genes linked to loss of alternative developmental potentials and B-lineage commitment. This review focuses on the molecular regulation of early B-lymphoid development and aims to provide an up to date summary of the current status of the research area.
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| 4. |
- Hallgren, Jenny, et al.
(författare)
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Pathways of murine mast cell development and trafficking : tracking the roots and routes of the mast cell
- 2007
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Ingår i: Immunological Reviews. - 0105-2896 .- 1600-065X. ; 217:1, s. 8-18
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Forskningsöversikt (refereegranskat)abstract
- The appreciation of the role of the mast cell (MC) in inflammatory processes has expanded dramatically during the last decade. Many of these processes, especially more prolonged responses, are accompanied by an increase in the number of MCs, and much of this increase is likely because of recruitment of immature progenitors with subsequent maturation under the control of the tissue microenvironment. We have begun to identify many of the cell-surface molecules that control this influx and have traced the development of these cells back to their hematopoietic roots. This development proceeds along the myelomonocytic pathway with distinct intermediates having been identified in both bone marrow and spleen. The expression of alpha4beta7 integrins has played a prominent role in this process, as it helped identify a bipotent basophil MC precursor in the spleens of C57BL/6 mice. This integrin also controls basal influx into the intestine and, along with alpha4beta1 integrins, plays a critical role in recruitment to inflamed lungs. Investigation of chemokines and chemokine receptors in these processes led to the identification of a dual role for the murine interleukin-8 receptor CXCR2. This alpha-chemokine receptor affects MC progenitor trafficking by its expression by MC progenitors and by its expression on stromal cells, likely endothelium, affecting trafficking to both intestine under basal conditions and lung during inflammatory recruitment.
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| 5. |
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| 7. |
- Milling, Simon, et al.
(författare)
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Subsets of migrating intestinal dendritic cells.
- 2010
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Ingår i: Immunological reviews. - : Wiley. - 1600-065X .- 0105-2896. ; 234:1, s. 259-67
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Forskningsöversikt (refereegranskat)abstract
- Dendritic cells (DCs) in the intestine are heterogeneous. Phenotypically different populations of conventional DCs have been identified in the intestinal lamina propria, Peyer's patches, and in the draining mesenteric lymph nodes, to which these DCs constitutively migrate. Markers used to identify these populations include major histocompatibility complex class II, CD11c, CD8 alpha, CD11b, and CD103. Extensive studies in rats, summarized here, which involved collection of migrating DCs by thoracic duct cannulation after mesenteric lymphadenectomy, have clearly demonstrated that the subsets of migrating intestinal lymph DCs have different functional properties. The subsets might play different roles in the induction of oral tolerance and in driving systemic immune responses after vaccination or intestinal stimulation with Toll-like receptor ligands. The use of these surgical techniques allows investigation of the functions of purified subsets of migrating DCs. However, in the rat, these studies are limited by the range of available reagents and are difficult to compare with data from other species in this fast-moving field. Recent refinements have enabled the collection of migrating intestinal DCs from mice; our initial results are described here. We believe that these studies will generate exciting data and have the potential to resolve important questions about the functions of migrating intestinal DC subsets.
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| 8. |
- Uysal, Hüseyin, et al.
(författare)
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Antibodies to citrullinated proteins : molecular interactions and arthritogenicity
- 2010
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Ingår i: Immunological Reviews. - Hoboken, NJ : Wiley-Blackwell Publishing Inc.. - 0105-2896 .- 1600-065X. ; 233:1, s. 9-33
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of antibodies specific for citrullinated protein epitopes [anti-citrullinated protein antibodies (ACPAs)] is a hallmark for the diagnosis and prognosis of rheumatoid arthritis (RA) and will also be a useful tool for understanding the fundamental pathologic processes. There are several essential questions pertaining to ACPA that remain to be explored, such as understanding the early specificity of the underlying T-cell recognition, whether the production of ACPA is a primary or secondary process, and in the event of such antibodies being arthritogenic, whether they could possibly regulate the disease development. To answer these questions, animal models are needed, but unfortunately ACPA is not a prominent feature of any of the classical animal models of RA. However, we showed recently that ACPA can be isolated from animals susceptible to collagen-induced arthritis that are specific for citrullinated type II collagen (CII). The citrulline specificity could be visualized, and the specificity is determined primarily by a direct interaction with citrulline. We also demonstrated that these antibodies are specific for the citrullinated epitopes and are pathogenic in vivo. A new hypothesis to explain how inflammation in RA can be directed to cartilaginous joints and be self-perpetuating is suggested, which involves recognition of post-translational modifications (glycosylation and citrullination) on CII by T and B cells that can have both arthritogenic and regulatory consequences. © 2009 John Wiley & Sons A/S.
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| 9. |
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| 10. |
- Bekiaris, Vasileios, et al.
(författare)
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Intestinal dendritic cells in the regulation of mucosal immunity.
- 2014
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Ingår i: Immunological Reviews. - : Wiley. - 1600-065X .- 0105-2896. ; 260:1, s. 86-101
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Forskningsöversikt (refereegranskat)abstract
- The intestine presents a huge surface area to the outside environment, a property that is of critical importance for its key functions in nutrient digestion, absorption, and waste disposal. As such, the intestine is constantly exposed to dietary and microbial-derived foreign antigens, to which immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive immune responses. In the intestinal mucosa, DCs are located diffusely throughout the intestinal lamina propria, within gut-associated lymphoid tissues, including Peyer's patches and smaller lymphoid aggregates, as well as in intestinal-draining lymph nodes, including mesenteric lymph nodes. The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality of intestinal DCs. In the current review, we discuss recent findings from our group and others that have provided important insights regarding murine and human intestinal lamina propria DCs and highlighted marked developmental and functional heterogeneity within this compartment. A thorough understanding of the role these subsets play in the regulation of intestinal immune homeostasis and inflammation will help to define novel strategies for the treatment of intestinal pathologies and contribute to improved rational design of mucosal vaccines.
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