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Ardesjö, Brita
Alternative names
Publications (10 of 14) Show all publications
Tengvall, K., Bergvall, K., Olsson, M., Ardesjö-Lundgren, B., Farias, F. H., Kierczak, M., . . . Andersson, G. (2020). Transcriptomes from German shepherd dogs reveal differences in immune activity between atopic dermatitis affected and control skin. Immunogenetics, 72(5), 315-323
Open this publication in new window or tab >>Transcriptomes from German shepherd dogs reveal differences in immune activity between atopic dermatitis affected and control skin
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2020 (English)In: Immunogenetics, ISSN 0093-7711, E-ISSN 1432-1211, Vol. 72, no 5, p. 315-323Article in journal (Refereed) Published
Abstract [en]

Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease with both genetic and environmental risk factors described. We performed mRNA sequencing of non-lesional axillary skin biopsies from nine German shepherd dogs. Obtained RNA sequences were mapped to the dog genome (CanFam3.1) and a high-quality skin transcriptome was generated with 23,510 expressed gene transcripts. Differentially expressed genes (DEGs) were defined by comparing three controls to five treated CAD cases. Using a leave-one-out analysis, we identified seven DEGs: five known to encode proteins with functions related to an activated immune system (CD209, CLEC4G, LOC102156842 (lipopolysaccharide-binding protein-like), LOC480601 (regakine-1-like), LOC479668 (haptoglobin-like)), one (OBP) encoding an odorant-binding protein potentially connected to rhinitis, and the last (LOC607095) encoding a novel long non-coding RNA. Furthermore, high mRNA expression of inflammatory genes was found in axillary skin from an untreated mild CAD case compared with healthy skin. In conclusion, we define genes with different expression patterns in CAD case skin helping us understand post-treatment atopic skin. Further studies in larger sample sets are warranted to confirm and to transfer these results into clinical practice.

Keywords
Canine atopic dermatitis, Differential gene expression, Skin transcriptome, mRNA sequencing
National Category
Veterinary Science Medical Genetics
Identifiers
urn:nbn:se:uu:diva-420920 (URN)10.1007/s00251-020-01169-3 (DOI)000541211900001 ()32556497 (PubMedID)
Funder
Swedish Research Council, 524-2012-7053
Available from: 2020-10-02 Created: 2020-10-02 Last updated: 2020-11-25Bibliographically approved
Ardesjö-Lundgren, B., Tengvall, K., Bergvall, K., Farias, F. H. G., Wang, L., Hedhammar, Å., . . . Andersson, G. (2017). Comparison of cellular location and expression of Plakophilin-2 in epidermal cells from nonlesional atopic skin and healthy skin in German shepherd dogs. Veterinary dermatology (Print), 28(4), 377-e88
Open this publication in new window or tab >>Comparison of cellular location and expression of Plakophilin-2 in epidermal cells from nonlesional atopic skin and healthy skin in German shepherd dogs
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2017 (English)In: Veterinary dermatology (Print), ISSN 0959-4493, E-ISSN 1365-3164, Vol. 28, no 4, p. 377-e88Article in journal (Refereed) Published
Abstract [en]

Background

Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease caused by interactions between genetic and environmental factors. Previously, a genome‐wide significant risk locus on canine chromosome 27 for CAD was identified in German shepherd dogs (GSDs) and Plakophilin‐2 (PKP2) was defined as the top candidate gene. PKP2 constitutes a crucial component of desmosomes and also is important in signalling, metabolic and transcriptional activities.

Objectives

The main objective was to evaluate the role of PKP2 in CAD by investigating PKP2 expression and desmosome structure in nonlesional skin from CAD‐affected (carrying the top GWAS SNP risk allele) and healthy GSDs. We also aimed at defining the cell types in the skin that express PKP2 and its intracellular location.

Animals/Methods

Skin biopsies were collected from nine CAD‐affected and five control GSDs. The biopsies were frozen for immunofluorescence and fixed for electron microscopy immunolabelling and morphology.

Results

We observed the novel finding of PKP2 expression in dendritic cells and T cells in dog skin. Moreover, we detected that PKP2 was more evenly expressed within keratinocytes compared to its desmosomal binding‐partner plakoglobin. PKP2 protein was located in the nucleus and on keratin filaments attached to desmosomes. No difference in PKP2 abundance between CAD cases and controls was observed.

Conclusion

Plakophilin‐2 protein in dog skin is expressed in both epithelial and immune cells; based on its subcellular location its functional role is implicated in both nuclear and structural processes.

National Category
Veterinary Science
Identifiers
urn:nbn:se:uu:diva-333703 (URN)10.1111/vde.12441 (DOI)000407137900010 ()28386956 (PubMedID)
Funder
Swedish Research Council, 521-2012-2826, 221-2009-1689, 524-2012-7053EU, European Research Council, 310203
Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2020-10-01Bibliographically approved
Oftedal, B. E., Ardesjö Lundgren, B., Bratland, E., Wolff, A. B., Hamm, D., Gan, P.-Y., . . . Scott, H. S. (2017). T cell receptor assessment in autoimmune disease requires access to the most adjacent immunologically active organ. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 326-326
Open this publication in new window or tab >>T cell receptor assessment in autoimmune disease requires access to the most adjacent immunologically active organ
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 326-326Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-346966 (URN)000411865200186 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-03-23Bibliographically approved
Tengvall, K., Kozyrev, S., Kierczak, M., Bergvall, K., Farias, F. H. G., Ardesjö-Lundgren, B., . . . Lindblad-Toh, K. (2016). Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs. BMC Genetics, 17(1), Article ID 97.
Open this publication in new window or tab >>Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs
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2016 (English)In: BMC Genetics, E-ISSN 1471-2156, Vol. 17, no 1, article id 97Article in journal (Refereed) Published
Abstract [en]

Background

Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2.

Results

Additional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 × 10−7) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 × 10−5), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region.

Conclusions

Our experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.

Keywords
PKP2, Atopic dermatitis, Genetic association, Luciferase reporter assay, Cell type-specific enhancers, Dog, Plakophilin 2, Eczema
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-299868 (URN)10.1186/s12863-016-0404-3 (DOI)000378844000003 ()27357287 (PubMedID)
Funder
Swedish Research Council, 521-2012-2826Swedish Research Council Formas, 221-2009-1689EU, European Research Council, 310203EU, FP7, Seventh Framework Programme, GA-201370
Available from: 2016-07-28 Created: 2016-07-28 Last updated: 2024-01-17Bibliographically approved
Hardtke-Wolenski, M., Taubert, R., Noyan, F., Sievers, M., Dywicki, J., Schlue, J., . . . Jaeckel, E. (2015). Autoimmune Hepatitis in a Murine Autoimmune Polyendocrine Syndrome Type 1 Model Is Directed Against Multiple Autoantigens. Hepatology, 61(4), 1295-1305
Open this publication in new window or tab >>Autoimmune Hepatitis in a Murine Autoimmune Polyendocrine Syndrome Type 1 Model Is Directed Against Multiple Autoantigens
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2015 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 61, no 4, p. 1295-1305Article in journal (Refereed) Published
Abstract [en]

Autoimmune polyendocrine syndrome type 1 (APS-1) is caused by mutations of the autoimmune regulator (AIRE) gene. Mouse studies have shown that this results in defective negative selection of T cells and defective early seeding of peripheral organs with regulatory T cells (Tregs). Aire deficiency in humans and mice manifests as spontaneous autoimmunity against multiple organs, and 20% of patients develop an autoimmune hepatitis (AIH). To study AIH in APS-1, we generated a murine model of human AIH on a BALB/c mouse background, in which Aire is truncated at exon 2. A subgroup of 24% of mice is affected by AIH, characterized by lymphoplasmacytic and periportal hepatic infiltrates, autoantibodies, elevated aminotransferases, and a chronic and progressive course of disease. Disease manifestation was dependent on specific Aire mutations and the genetic background of the mice. Though intrahepatic Treg numbers were increased and hyperproliferative, the intrahepatic CD4/CD8 ratio was decreased. The targets of the adaptive autoimmune response were polyspecific and not focussed on essential autoantigens, as described for other APS-1-related autoimmune diseases. The AIH could be treated with prednisolone or adoptive transfer of polyspecific Tregs. Conclusion: Development of AIH in APS-1 is dependent on specific Aire mutations and genetic background genes. Autoimmune response is polyspecific and can be controlled by steroids or transfer with Tregs. This might enable new treatment options for patients with AIH.

National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-252187 (URN)10.1002/hep.27639 (DOI)000352099700025 ()25475693 (PubMedID)
Available from: 2015-05-06 Created: 2015-05-04 Last updated: 2017-12-04Bibliographically approved
Isaksson, M., Ardesjö Lundgren, B., Ahlgren, K. M., Kämpe, O. & Lobell, A. (2012). Conditional DC depletion does not affect priming of encephalitogenic Th cells in EAE. European Journal of Immunology, 42(10), 2555-2563
Open this publication in new window or tab >>Conditional DC depletion does not affect priming of encephalitogenic Th cells in EAE
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2012 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 42, no 10, p. 2555-2563Article in journal (Refereed) Published
Abstract [en]

EAE, an animal model for multiple sclerosis, is a Th17- and Th1-cell-mediated auto-immune disease, but the mechanisms leading to priming of encephalitogenicTcells in autoimmune neuroinflammation are poorly understood. To investigate the role of dendritic cells (DCs) in the initiation of autoimmuneTh17- andTh1-cell responses andEAE, we used mice transgenic for a simian diphtheria toxin receptor (DTR) expressed under the control of the murineCD11c promoter (CD11c-DTRmice onC57BL/6 background).EAEwas induced by immunization with myelin oligodendrocyte glycoprotein (MOG) protein in CFA. DCs were depleted on the day before and 8 days afterMOG immunization. The mean clinicalEAEscore was only mildly reduced inDC-depleted mice when DCs were ablated beforeEAEinduction. The frequency of activatedTh cells was not altered, andMOG-inducedTh17 orTh1-cell responses were not altered, in the spleens ofDC-depleted mice. Similar results were obtained ifDCswere ablated the first 10 days afterMOGimmunization with repeatedDCdepletions. Unexpectedly, transient depletion of DCs did not affect priming or differentiation of MOG-inducedTh17 andTh1-cell responses or the incidence ofEAE. Thus, the mechansim of priming ofTh cells inEAEremains to be elucidated.

National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-173266 (URN)10.1002/eji.201142239 (DOI)000309610200004 ()22806332 (PubMedID)
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2012-04-23 Created: 2012-04-21 Last updated: 2020-11-04Bibliographically approved
Ardesjö, B., Portela-Gomes, G. M., Rorsman, F., Grimelius, L. & Ekwall, O. (2010). Identification of a novel staining pattern of bile duct epithelial cells in primary sclerosing cholangitis. Inflammatory Bowel Diseases, 16(2), 305-311
Open this publication in new window or tab >>Identification of a novel staining pattern of bile duct epithelial cells in primary sclerosing cholangitis
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2010 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 16, no 2, p. 305-311Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Primary sclerosing cholangitis (PSC) is an inflammatory disease of the bile ducts with an unknown etiology. A number of autoantigens have been proposed, but an early diagnostic marker is still lacking. Our aim was to identify such an autoantigen. METHODS: Immunostaining was performed on normal human bile duct with sera from patients with PSC and controls. To identify an autoantigen a cDNA library from normal human choledochus was constructed and immunoscreened with patient sera. Using in vitro transcription and translation and immunoprecipitation we examined the immunoreactivity against PDZ domain containing 1 (PDZK1) in 35 patients with PSC, 198 control patients, and 94 healthy controls. RESULTS: We observed a previously unpublished staining pattern in which cytoplasmatic granules and apical cell membranes of biliary epithelial cells were stained by PSC sera. Strong immunoreactivity to these structures was obtained with 12 out of 35 PSC sera (34%) but not with sera from healthy controls. By screening the cDNA library we identified PDZK1 as a candidate antigen. Immunoreactivity against PDZK1 was detected in 9% of PSC patients, 2% of inflammatory bowel disease (IBD) patients, 8% of autoimmune pancreatitis patients, 18% of Grave's disease patients, and 1% of healthy controls. CONCLUSIONS: Previously unpublished, specific, and strong autoantibodies against epithelial cells of the bile duct in PSC sera were identified. Furthermore, PDZK1 is suggested as a potential new autoantigen.

Keywords
PDZK1, Primary sclerosing cholangitis, autoantigens, bile duct, epithelial cells
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-124967 (URN)10.1002/ibd.21050 (DOI)000274911200022 ()19653288 (PubMedID)
Available from: 2010-05-06 Created: 2010-05-06 Last updated: 2022-01-28Bibliographically approved
Ardesjö Lundgren, B., Rorsman, F., Portela-Gomes, G. M., Grimelius, L., Ekdahl, K. N., Nilsson, B. & Ekwall, O. (2010). Identification of complement C3 as an autoantigen in inflammatory bowel disease. European Journal of Gastroenterology and Hepathology, 22(4), 429-436
Open this publication in new window or tab >>Identification of complement C3 as an autoantigen in inflammatory bowel disease
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2010 (English)In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 22, no 4, p. 429-436Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Autoantibodies against goblet cells in the gastrointestinal mucosa have been described in patients with inflammatory bowel disease (IBD) but a corresponding autoantigen has not yet been identified. The aim of this study was to identify such an antigen. METHODS: First, 10 candidate autoantigens were discarded based on double stainings of appendiceal sections and a mucin-producing cell line (HT29-mtx). Second, an appendiceal cDNA library was immunoscreened with IBD sera. RESULTS: Three out of 48 positive clones were identified as complement C3. Using immunoprecipitation of in vitro transcribed and translated C3, seven of 17 primary sclerosing cholangitis patient sera, 15 of 65 IBD sera, and none out of 54 sera from healthy blood donors showed C3 immunoreactivity. The results were confirmed using western blot and an enzyme-linked immunosorbent assay with alternative sources of C3 protein. CONCLUSION: In conclusion, we have identified complement C3 as a potential autoantigen in IBD and primary sclerosing cholangitis.

National Category
Gastroenterology and Hepatology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-124296 (URN)10.1097/MEG.0b013e32833283b1 (DOI)000276566100007 ()19829122 (PubMedID)
Available from: 2010-05-03 Created: 2010-05-03 Last updated: 2022-01-28Bibliographically approved
Isaksson, M., Ardesjö, B., Rönnblom, L., Kämpe, O., Lassmann, H., Eloranta, M.-L. & Lobell, A. (2009). Plasmacytoid DC promote priming of autoimmune Th17 cells and EAE. European Journal of Immunology, 39(10), 2925-2935
Open this publication in new window or tab >>Plasmacytoid DC promote priming of autoimmune Th17 cells and EAE
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2009 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 39, no 10, p. 2925-2935Article in journal (Refereed) Published
Abstract [en]

EAE, an animal model for MS, is a Th17 and Th1-cell-mediated autoimmune disease, but the mechanisms leading to priming of encephalitogenic T cells in autoimmune neuroinflammation are poorly understood. To investigate the role of plasmacytoid DC (pDC) in the initiation of autoimmune Th17- and Th1-cell responses and EAE, we depleted pDC with anti-pDC Ag-1 (anti-PDCA1) mAb prior to immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein (MOG). pDC-depleted mice developed less severe clinical and histopathological signs of EAE than control mice, which demonstrates a promoting role for pDC in the initiation of EAE. The levels of type I IFN were much lower in the sera from anti-PDCA1-treated mice. However, neutralization of type I IFN ameliorated the early phase of EAE but did not alter the severity of disease. Thus, only a minor part of the EAE-promoting effect of pDC appears to be mediated by IFN-alpha/beta secretion. The numbers of MOG-specific Th17 cells, but not Th1 cells, were lower in spleen from anti-PDCA1-treated mice compared with controls. In contrast, pDC depletion a week after MOG immunization resulted in more severe clinical signs of EAE. In conclusion, we demonstrate that pDC promote initiation of MOG-induced Th17-cell responses and EAE.

Keywords
Autoimmunity, DC, EAE/MS, T cells, Type I IFN
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-108362 (URN)10.1002/eji.200839179 (DOI)000271151000030 ()19637225 (PubMedID)
Available from: 2009-09-16 Created: 2009-09-16 Last updated: 2022-01-28Bibliographically approved
Ardesjö, B., Hansson, C. M., Bruder, C. E. .., Rorsman, F., Betterle, C., Dumanski, J. P., . . . Ekwall, O. (2008). Autoantibodies to Glutathione S-transferase theta 1 in patients with primary sclerosing cholangitis and other autoimmune diseases. Journal of Autoimmunity, 30(4), 273-282
Open this publication in new window or tab >>Autoantibodies to Glutathione S-transferase theta 1 in patients with primary sclerosing cholangitis and other autoimmune diseases
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2008 (English)In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 30, no 4, p. 273-282Article in journal (Refereed) Published
Abstract [en]

Primary sclerosing cholangitis (PSC) is an enigmatic disorder with a suggested autoimmune basis. A variety of autoantigens have been suggested but no specific or highly directed epitope has been identified. To address this issue, we constructed a cDNA library from normal human choledochus and screened expressing clones with serum from a patient with PSC and inflammatory bowel disease (IBD). Based on this screening, glutathione S-transferase theta 1 (GSTT1) was identified as a potential autoantigenic target. To study the specificity of GSTT1, we determined immunoreactivity using a panel of 58 patients with PSC, with and without IBD, 57 patients with IBD, 31 patients with Hashimoto's thyroiditis, 30 patients with primary biliary cirrhosis (PBC), 20 patients with insulin dependent diabetes mellitus, 22 patients with autoimmune polyendocrine syndrome type 1, 10 patients with systemic lupus erythematosus (SLE), 20 patients with Sjogren's syndrome, 12 patients with autoimmune pancreatitis, 28 patients with Addison's disease, 27 patients with Grave's disease, 17 with myasthenia gravis, and 118 healthy controls. Reactivity against GSTT1 was found with PSC and IBD as well as some patients with other autoimmune pathology, indicating that this population of antibodies is neither specific nor a sensitive serologic marker for PSC, but the frequency was clearly higher in autoimmune patients than controls. GSTT1-antibodies have been described in persons with GSTT1-null genotype and are suggested to develop as an alloimmune response to blood transfusions from GSTT1-positive donors or pregnancies with GSTT1-positive children. Therefore, two IBD patients with and 15 PSC patients without GSTT1-antibodies were genotyped for GSTT1 to investigate if the presence of GSTT1-antibodies was associated with the GSTT1-null genotype and possibly caused by an alloimmune response. Both IBD patients and three of the PSC patients were of the GSTT1-null genotype. We note that the frequency of GSTT1-antibodies in this study is more than 100-fold higher than the frequency described earlier in patients with autoimmune diseases. We also observe an increased frequency of GSTT1-antibodies in patients with autoimmune diseases compared to healthy controls. This increased frequency can be explained by an autoimmune phenotype which increases susceptibility to such autoantibodies, or by a high frequency of the GSTT1-null genotype in autoimmune disease.

Keywords
autoantibodies, copy number variation, glutathione S-transferase theta 1, PCR product based array-CGH, primary sclerosing cholangitis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-97136 (URN)10.1016/j.jaut.2007.11.008 (DOI)000255834500010 ()18242955 (PubMedID)
Available from: 2008-04-24 Created: 2008-04-24 Last updated: 2022-01-28Bibliographically approved
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