| 1. |
- Abolhalaj, Milad, et al.
(författare)
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Profiling dendritic cell subsets in head and neck squamous cell tonsillar cancer and benign tonsils.
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:8030
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) have a key role in orchestrating immune responses and are considered important targets for immunotherapy against cancer. In order to develop effective cancer vaccines, detailed knowledge of the micromilieu in cancer lesions is warranted. In this study, flow cytometry and human transcriptome arrays were used to characterize subsets of DCs in head and neck squamous cell tonsillar cancer and compare them to their counterparts in benign tonsils to evaluate subset-selective biomarkers associated with tonsillar cancer. We describe, for the first time, four subsets of DCs in tonsillar cancer: CD123+ plasmacytoid DCs (pDC), CD1c+, CD141+, and CD1c-CD141- myeloid DCs (mDC). An increased frequency of DCs and an elevated mDC/pDC ratio were shown in malignant compared to benign tonsillar tissue. The microarray data demonstrates characteristics specific for tonsil cancer DC subsets, including expression of immunosuppressive molecules and lower expression levels of genes involved in development of effector immune responses in DCs in malignant tonsillar tissue, compared to their counterparts in benign tonsillar tissue. Finally, we present target candidates selectively expressed by different DC subsets in malignant tonsils and confirm expression of CD206/MRC1 and CD207/Langerin on CD1c+ DCs at protein level. This study descibes DC characteristics in the context of head and neck cancer and add valuable steps towards future DC-based therapies against tonsillar cancer.
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| 2. |
- Askmyr, David, et al.
(författare)
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Pattern recognition receptor expression and maturation profile of dendritic cell subtypes in human tonsils and lymph nodes
- 2021
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Ingår i: Human Immunology. - : Elsevier BV. - 0198-8859. ; 82:12, s. 976-981
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) with capacity of antigen cross-presentation are of key interest for immunotherapy against cancer as they can induce antigen-specific cytotoxic T lymphocyte (CTL) responses. This study describes frequencies of DC subtypes in human tonsils and lymph nodes, and phenotypic aspects that may be targeted by adjuvant measures. From human tonsils and neck lymph nodes, DCs were identified through flow cytometry, and subsets of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were investigated. Maturity status was assessed and surface receptors with CTL-promoting potentials were studied. CD123+ pDCs as well as CD1c+, CD141+, and CD1c-CD141- mDCs were detected in tonsils and lymph nodes. Both sites featured a similar presence of DC subsets, with CD123+ pDC being dominant and CD141+ mDCs least frequent. Based on CD80/CD86 expression, all DC subtypes featured a low degree of maturation. Expression of pattern recognition receptors (PRRs) CD206, CD207, DC-SIGN, TLR2, and TLR4, as well as the chemokine receptor XCR1, indicated DC subset-specific receptor profiles. We conclude that tonsils and lymph nodes share common features in terms of DC subset frequency and maturation as well as PRR and XCR1 expression pattern. Our work suggests that both sites may be considered for vaccine deposition in DC-mediated immunotherapy.
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| 3. |
- Broos, Sissela, et al.
(författare)
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Immunomodulatory nanoparticles as adjuvants and allergen-delivery system to human dendritic cells: Implications for specific immunotherapy.
- 2010
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 28, s. 5075-5085
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Tidskriftsartikel (refereegranskat)abstract
- Novel adjuvants and antigen-delivery systems with immunomodulatory properties that shift the allergenic Th2 response towards a Th1 or regulatory T cell response are desired for allergen-specific immunotherapy. This study demonstrates that 200-nm sized biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs) are activators of human monocyte-derived dendritic cells (MoDCs). gamma-PGA NPs are efficiently internalized by immature MoDCs and strongly stimulate production of chemokines and inflammatory cytokines as well as up-regulation of co-stimulatory molecules and immunomodulatory mediators involved in efficient T cell priming. Furthermore, MoDCs from allergic subjects stimulated in vitro with a mixture of gamma-PGA NPs and extract of grass pollen allergen Phleum pratense (Phl p) augment allergen-specific IL-10 production and proliferation of autologous CD4(+) memory T cells. Thus, gamma-PGA NPs are promising as sophisticated adjuvants and allergen-delivery systems in allergen-specific immunotherapy.
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| 4. |
- Larsson, Kristina, et al.
(författare)
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CD4+ T-cells have a key instructive role in educating dendritic cells in allergy
- 2009
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 149:1, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dendritic cells (DCs) are central in allergy as regulators of the Th1/Th2 balance. We have recently demonstrated a unique transcriptional profile of DCs in patients with ongoing allergy compared with healthy subjects and shown that crosstalk between DCs and memory T cells affects the transcriptional profile of T cells. However, the transcriptional profile of DCs educated by T cells in allergy is unknown. Methods: In the present study, we have examined the transcriptional profiles of DCs after stimulation with grass pollen allergens, Phleum pratense and coculture with autologous CD4+ memory T cells using high-density microarray. Protein analysis was performed using flow cytometry and recombinant antibody protein microarrays. Patients with allergic rhinitis and healthy subjects were compared. Results: The results reveal a distinct T-cell-induced DC profile in atopic individuals. Accordingly, about 170 genes were upregulated and 40 genes downregulated. For example, the chemokine receptor CXCR4 and the tumor necrosis factor receptor CD30 were upregulated in DCs derived from atopic donors, and this could also be verified at the protein level. Conclusion: We conclude that crosstalk between CD4+ memory T cells and autologous DCs induces transcriptional reprogramming in DCs. This finding suggests that T cells have a key instructive role in educating DCs in Th2-type responses.
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| 5. |
- Lundberg, Kristina, et al.
(författare)
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Allergen-Specific Immunotherapy Alters the Frequency, as well as the FcR and CLR Expression Profiles of Human Dendritic Cell Subsets.
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Allergen-specific immunotherapy (AIT) induces tolerance and shifts the Th2 response towards a regulatory T-cell profile. The underlying mechanisms are not fully understood, but dendritic cells (DC) play a vital role as key regulators of T-cell responses. DCs interact with allergens via Fc receptors (FcRs) and via certain C-type lectin receptors (CLRs), including CD209/DC-SIGN, CD206/MR and Dectin-2/CLEC6A. In this study, the effect of AIT on the frequencies as well as the FcR and CLR expression profiles of human DC subsets was assessed. PBMC was isolated from peripheral blood from seven allergic donors before and after 8 weeks and 1 year of subcutaneous AIT, as well as from six non-allergic individuals. Cells were stained with antibodies against DC subset-specific markers and a panel of FcRs and CLRs and analyzed by flow cytometry. After 1 year of AIT, the frequency of CD123+ DCs was increased and a larger proportion expressed FcεRI. Furthermore, the expression of CD206 and Dectin-2 was reduced on CD141+ DCs after 1 year of treatment and CD206 as well as Dectin-1 was additionally down regulated in CD1c+ DCs. Interestingly, levels of DNGR1/CLEC9A on CD141+ DCs were increased by AIT, reaching levels similar to cells isolated from non-allergic controls. The modifications in phenotype and occurrence of specific DC subsets observed during AIT suggest an altered capacity of DC subsets to interact with allergens, which can be part of the mechanisms by which AIT induces allergen tolerance.
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| 6. |
- Lundberg, Kristina, et al.
(författare)
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Augmented Phl p 5-specific Th2 response after exposure of Dendritic Cells to allergen in complex with specific IgE compared to IgG1 and IgG4
- 2008
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616. ; 128:3, s. 358-365
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Tidskriftsartikel (refereegranskat)abstract
- In this study we have elucidated the effects of allergen-specific antibodies on human DCs and T-cells. Monocyte-derived DCs from allergic patients were exposed to Phlp 5 alone or in complex with Phlp 5-specific human IgG1, IgG4 or IgE and further co-cultured with autologous memory CD4+ T-cells. We demonstrate that DCs treated with Phlp 5/IgE-complexes secrete higher levels of IL-1a, IL-6, VEGF and MCP-3 compared to Phlp 5 alone. Furthermore, we show that the ability of DCs to present allergen to memory CD4+ T-cells and induce a Th2 cytokine profile is significantly augmented when the uptake is mediated by specific IgE antibodies, whereas IgG1 and IgG4 have no such effect. The differences in cytokine profiles depending on the antibody subtype could partly explain the ability of allergic individuals to amplify allergen-specific immune response and could thus be involved in the etiology of allergic responses.
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| 7. |
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| 8. |
- Lundberg, Kristina, et al.
(författare)
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Fc epsilon RI levels and frequencies of peripheral blood dendritic cell populations in allergic rhinitis
- 2010
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Ingår i: Human Immunology. - : Elsevier BV. - 0198-8859. ; 71:10, s. 931-933
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Tidskriftsartikel (refereegranskat)abstract
- The dendritic cell (DC) lineage encompasses a diverse population of cells with unique subtype-specific functions. In peripheral blood, four DC subsets have been identified based on their distinct expression of CD1c, CD141, CD16, and CD123, and these subpopulations exhibit functional properties in immune responses. However, their respective roles in allergic diseases, such as rhinitis, are unclear. In this study, we have performed comparative assessments of DC subset frequencies and investigated their Fc epsilon RI expression levels in patients with allergic rhinitis. We demonstrate that the frequencies of CD1c(+) and CD141(+) DCs are elevated in grass pollen-allergic subjects compared with healthy controls, irrespectively of allergen stimulation. Among the DC subsets, CD1c(+) DCs expressed the highest levels of Fc epsilon RI mRNA, and a large proportion expressed surface Fc epsilon RI. Furthermore, the Fc epsilon RI expression levels were augmented upon allergen challenge. Thus our data suggest that CD1c(+) DCs influence allergen-specific immune responses. Research on their functional properties in allergy is warranted for development of future immunotherapies targeting specialized DC subsets. (C) 2010 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and immunogenetics.
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| 9. |
- Lundberg, Kristina, et al.
(författare)
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Histamine H(4) receptor antagonism inhibits allergen-specific T-cell responses mediated by human dendritic cells.
- 2011
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 651:1-3, s. 197-204
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells are potential targets in allergy therapy as they, under the influence of their microenvironment, regulate T-cell responses. Histamine has been shown to promote Th2 polarization by dendritic cells. However, neither the mechanism nor the functionality of the different histamine receptors in this process has been fully elucidated. The aim of the present study was to identify factors involved in histamine-mediated dendritic cell activation as well as to study dendritic cell expression of histamine H(1) and H(4) receptors and their influence on allergen-specific T-cell responses in grass pollen allergy. Assessment of dendritic cell gene regulation by histamine using mRNA microarrays demonstrated that histamine alters many immunoregulatory genes of which the majority are novel in this context. Additionally, immunocytochemical stainings showed protein expression of histamine H(1) and H(4) receptors on dendritic cells from healthy and allergic donors. Furthermore, histamine H(1) and H(4) receptor antagonists (pyrilamine/N-(4-methoxybenzyl)-N',N'-dimethyl-N-pyridin-2-ylethane-1,2-diamine and JNJ7777120/1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine, respectively) were shown to influence histamine-induced dendritic cell maturation. Interestingly, JNJ7777120 inhibited dendritic cells' capacity to induce allergen-specific T-cell proliferation. In conclusion, H(4) receptor antagonism suppressed DC-induced, allergen-specific T-cell responses in humans and might thus inhibit allergic responses. This finding indicates that the H(4) receptor is a potential treatment target in human allergic conditions.
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| 10. |
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