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- 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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| 3. |
- 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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| 6. |
- 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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| 7. |
- Bemark, Mats, 1967, et al.
(författare)
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Know your enemy or find your friend?-Induction of IgA at mucosal surfaces.
- 2021
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Ingår i: Immunological reviews. - : Wiley. - 1600-065X .- 0105-2896. ; 303:1, s. 83-102
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Forskningsöversikt (refereegranskat)abstract
- Most antibodies produced in the body are of the IgA class. The dominant cell population producing them are plasma cells within the lamina propria of the gastrointestinal tract, but many IgA-producing cells are also found in the airways, within mammary tissues, the urogenital tract and inside the bone marrow. Most IgA antibodies are transported into the lumen by epithelial cells as part of the mucosal secretions, but they are also present in serum and other body fluids. A large part of the commensal microbiota in the gut is covered with IgA antibodies, and it has been demonstrated that this plays a role in maintaining a healthy balance between the host and the bacteria. However, IgA antibodies also play important roles in neutralizing pathogens in the gastrointestinal tract and the upper airways. The distinction between the two roles of IgA - protective and balance-maintaining - not only has implications on function but also on how the production is regulated. Here, we discuss these issues with a special focus on gut and airways.
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| 8. |
- Bergström, Tomas, et al.
(författare)
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Phylogenetic history of hominoid DRB loci and alleles inferred from intron sequences.
- 1999
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Ingår i: Immunol Rev. - 0105-2896. ; 167, s. 351-65
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Tidskriftsartikel (refereegranskat)abstract
- The evolutionary relationships among the MHC class II DRB4, DRB5 and DRB6 loci as well as the allelic lineages and alleles of the DRB1 locus were studied based on intron 1 and intron 2 sequences from humans, chimpanzee (Pan troglodytes), bonobo (Pan paniscus) and gorilla (Gorilla gorilla). The phylogenetic trees for these sequences indicate that most of the DRB1 allelic lineages predate the separation of the hominoid species studied, consistent with previous analysis of the coding sequences of these lineages. However, the intron sequence variation among alleles within DRB1 allelic lineages is very limited, consistent with the notion that the majority of the contemporary alleles have been generated within the last 250,000 years. The clustering of the DRB1 allelic lineages *08 and *12 with *03 supports a common ancestry for the DR8 and DR52 haplotypes. Similarly, the clustering of DRB1 allelic lineages *15 and *01 with the DRB3 locus is consistent with a common ancestry for the DR1 and DR51 haplotypes. Two cases of recombination around the second exon were observed: 1) the HLA-DRB6 locus appears to have been generated through a recombination between a DRB5 allele and an ancestral DRB6 allele, and 2) the gorilla sequence Gogo-DRB1 *03 appears to have been generated through a recombination between the DRB3 locus and an allele from the DRB1 *03 allelic lineage. The nucleotide substitution rate of DRB introns was estimated to 0.85-1.63 x 10(-9) per site per year, based on comparisons between the most closely related sequences from different hominoid species. This estimate is similar to the substitution rate for other intronic regions of the primate genome.
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