Simone Bürgler

University of Oslo, Kristiania (historical), Oslo, Norway

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Publications (6)44.39 Total impact

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    ABSTRACT: Background: Chronic rhinosinusitis (CRS) is characterized by epithelial activation and chronic T-cell infiltration in sinonasal mucosa and nasal polyps. IL-33 is a new cytokine of the IL-1 cytokine family that has a pro-inflammatory and Th2 type cytokine induction property. The role of IL-33 in the pathomechanisms of CRS and its interaction with other T cell subsets remain to be fully understood. Methods: The main trigger for IL-33 mRNA expression in primary human sinonasal epithelial cells was determined in multiple cytokine and T-cell stimulated cultures. The effects of IL-33 on naïve, Th0 and memory T-cells was studied by PCR, ELISA and flow cytometry. Biopsies from sinus tissue were analyzed by PCR and immunofluorescence for the presence of different cytokines and receptors with a special focus on IL-33. Results: IL-33 was mainly induced by IFN-γ in primary sinonasal epithelial cells, and induced a typical CRSwNP Th2 favoring cytokine profile upon co-culture with T-helper cell subsets. IL-33 and its receptor ST2 were highly expressed in the inflamed epithelial tissue of CRS patients. While IL-33 was significantly up-regulated in the epithelium for CRSsNP, its receptor was higher expressed in sinus tissue from CRSwNP. Conclusions: The present study delineates the influence of IL-33 in upper airway epithelium and a potential role of IL-33 in chronic inflammation of CRSwNP by enhancing Th2 type cytokine production, which could both contribute to a further increase of an established Th2 profile in CRSwNP.
    PLoS ONE 05/2015; 10(5):e0123163. DOI:10.1371/journal.pone.0123163 · 3.23 Impact Factor
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    ABSTRACT: Chronic lymphocytic leukemia (CLL) is a B cell malignancy associated with increased levels of inflammatory cytokines. Similarly, expression of CD38 on CLL cells correlates with CLL cell survival and proliferation, but the mechanisms that regulate CD38 expression and inflammatory cytokines remain unclear. We have recently demonstrated that patients have CLL-specific Th cells that support CLL proliferation. In this article, we show that CLL cells attract such Th cells, thereby establishing an Ag-dependent collaboration. Blocking experiments performed in vitro as wells as in vivo, using a xenograft model, revealed that secretion of IFN-γ was a major mechanism by which CLL-specific Th cells increased CD38 on CLL cells. The expression of the transcription factor T-bet in peripheral blood CLL cells significantly correlated with CD38 expression, and transient transfection of CLL cells with T-bet resulted in T-bet(hi)CD38(hi) cells. Finally, chromatin immunoprecipitation experiments revealed that T-bet can bind to regulatory regions of the CD38 gene. These data suggest that CLL cells attract CLL-specific Th cells and initiate a positive feedback loop with upregulation of T-bet, CD38, and type 1 chemokines allowing further recruitment of Th cells and increased type 1 cytokine secretion. This insight provides a cellular and molecular mechanism that links the inflammatory signature observed in CLL pathogenesis with CD38 expression and aggressive disease and suggests that targeting the IFN-γ/IFN-γR/JAK/STAT/T-bet/CD38 pathway could play a role in the therapy of CLL. Copyright © 2014 by The American Association of Immunologists, Inc.
    The Journal of Immunology 12/2014; 194(2). DOI:10.4049/jimmunol.1401350 · 4.92 Impact Factor
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    ABSTRACT: There is increasing interest in the chronic lymphocytic leukemia (CLL) microenvironment and the mechanisms that may promote CLL cell survival and proliferation. A role for T helper (Th) cells has been suggested, but current evidence is only circumstantial. Here we show that CLL patients had memory Th cells that were specific for endogenous CLL antigens. These Th cells activated autologous CLL cell proliferation in vitro and in human → mouse xenograft experiments. Moreover, CLL cells were efficient antigen-presenting cells that could endocytose and process complex proteins through antigen uptake pathways, including the B cell receptor. Activation of CLL cells by Th cells was contact and CD40L dependent. The results suggest that CLL is driven by ongoing immune responses related to Th cell-CLL cell interaction. We propose that Th cells support malignant B cells and that they could be targeted in the treatment of CLL.
    Cell Reports 08/2013; 4(3). DOI:10.1016/j.celrep.2013.07.011 · 8.36 Impact Factor
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    ABSTRACT: IL-32 is a proinflammatory cytokine involved in various chronic inflammatory diseases. Chronic airway inflammation in asthmatic patients results in structural airway changes, including angiogenesis. Vascular endothelial growth factor (VEGF) is a key inducer of angiogenesis in the airways of asthmatic patients. The aim of the study was to investigate the expression and function of IL-32 in patients with angiogenesis and asthma. The expression and regulation of IL-32 in normal human bronchial epithelial (NHBE) cells was analyzed by using RT-PCR, ELISA, Western blotting, immunofluorescent staining, and flow cytometry. After knockdown of IL-32 in NHBE cells by small interfering RNA (siRNA) transfections, VEGF secretion was quantified by means of ELISA. New blood vessel formation was determined with human umbilical vein endothelial cells by culturing with supernatants from IL-32 siRNA-transfected NHBE cells. IL-32 was determined in serum and induced sputum samples of asthmatic patients and healthy control subjects by means of ELISA. IL-32 is expressed in NHBE cells on stimulation with IFN-γ, TNF-α, T(H)1 cells, and rhinovirus. Inhibition of IL-32 expression resulted in significantly increased secretion of the proangiogenic factors VEGF and platelet-derived growth factor by NHBE cells. Human umbilical vein endothelial cells cultured in supernatants from IL-32 siRNA-transfected NHBE cells showed enhanced in vitro angiogenesis. IL-32 is detectable in induced sputum from asthmatic patients. IL-32 serum levels were significantly higher in asthmatic patients compared with those seen in healthy control subjects and correlated with response to asthma treatment. IL-32 is induced by IFN-γ, TNF-α, T(H)1 cells, and rhinovirus in bronchial epithelial cells. It inhibits angiogenesis, and its serum levels are associated with a good treatment response in asthmatic patients.
    The Journal of allergy and clinical immunology 02/2012; 129(4):964-73.e7. DOI:10.1016/j.jaci.2011.12.1002 · 11.48 Impact Factor
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    ABSTRACT: Keratinocyte (KC) apoptosis is an important mechanism of eczema and spongiosis in patients with atopic dermatitis (AD) and is mediated by IFN-gamma, which is secreted by T(H)1 cells. IL-32 is a proinflammatory cytokine that is involved in the inflammatory processes of rheumatoid arthritis, chronic obstructive pulmonary disease, and Crohn disease. Recently, it was shown that upregulation of IL-32 induces apoptosis. The aim of the study was to investigate the expression and function of IL-32 in patients with AD. The expression of IL-32 in KCs was analyzed by means of RT-PCR, ELISA, and flow cytometry. Transfections of small interfering RNA were performed in primary KCs, and apoptosis was analyzed by means of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, annexin-V, and 7-amino actinomycin D stainings. Immunofluorescence stainings were used to detect IL-32 in skin biopsy specimens, and serum levels of IL-32 were analyzed by means of ELISA. We report that IL-32 is expressed in human primary KCs on stimulation with IFN-gamma, TNF-alpha, and T(H)1 cells in contrast to T(H)2, regulatory T (Treg), or T(H)17 cells, which showed no effect. Transfection of primary KCs and artificial skin equivalents with small interfering RNA to IL-32, which resulted in a clear decrease in IL-32 expression, significantly reduced KC apoptosis. Immunofluorescence staining demonstrated that IL-32 was expressed in AD lesional skin, whereas it was present in neither skin biopsy specimens from healthy donors nor in lesional skin from patients with psoriasis. Serum levels of IL-32 from patients with AD correlated with disease severity, but increased serum levels of IL-32 were also detected in asthmatic patients. The present study demonstrates KCs as a source of IL-32, which modulates KC apoptosis and contributes to the pathophysiology of AD.
    The Journal of allergy and clinical immunology 03/2010; 125(4):858-865.e10. DOI:10.1016/j.jaci.2010.01.016 · 11.48 Impact Factor
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    ABSTRACT: Forkhead box p3 (FOXP3) is known to program the acquisition of suppressive capacities in CD4(+) regulatory T cells (Treg), whereas its role in CD8(+) T cells is unknown. The current study investigates whether FOXP3 also acts as a Treg master switch in peripheral blood and tonsillar CD8(+) T cells. Single-cell analyses reveal the existence of a FOXP3(+)CD8(+) population in human tonsils, whereas FOXP3(+)CD8(+) T cells are rarely detected in peripheral blood. Tonsillar FOXP3(+)CD8(+) T cells exhibit a Treg phenotype with high CTLA-4 and CD45RO and low CD127 and CD69 expression. Interestingly, the tonsillar FOXP3(+)CD8(+) T cells are mostly CD25(negative) and some cells also express the proinflammatory cytokines TNF-alpha, IFN-gamma, or IL-17A. Particularly, IL-17A-expressing cells are present among FOXP3(+)CD8(+) T cells. Even though FOXP3 expression is at the detection limit in peripheral blood CD8(+) T cells ex vivo, it can be induced in vitro in naive CD8(+) T cells by polyclonal stimulation. The induced FOXP3(+)CD8(+) T cells are predominantly CD25(high) and CD28(high) and similar to tonsillar cells, they produce high levels of TNF-alpha, IFN-gamma, and granzyme B. However, IL-4 expression is mutually exclusive and IL-17A expression is not detectable. These FOXP3(+)CD8(+) T cells suppress the proliferation of CD4(+) T cells in cocultures, while showing no direct cytotoxic activity. In conclusion, the current study characterizes FOXP3-expressing CD8(+) T cells from human tonsils and shows that in vitro activation leads to FOXP3 expression in CD8(+) T cells and gain of suppressive activity.
    The Journal of Immunology 03/2009; 182(4):2124-30. DOI:10.4049/jimmunol.0802271 · 4.92 Impact Factor

Publication Stats

158 Citations
44.39 Total Impact Points


  • 2013
    • University of Oslo
      • Department of Immunology (IMM)
      Kristiania (historical), Oslo, Norway
  • 2009-2010
    • University of Zurich
      • Swiss Institute of Allergy and Asthma Research - SIAF
      Zürich, Zurich, Switzerland