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  1. AU="Christoph Schlapbach"
  2. AU="Akbar, Shayista"
  3. AU="Butler, Eboneé N"
  4. AU="Moura-Alves, Márcio"
  5. AU="Marcet, Ismael"
  6. AU=Eichfelder Sebastian
  7. AU=Timins M E
  8. AU="Weber, Stephan"
  9. AU=Galuska David
  10. AU="Carrieri, Mariella"
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  1. Article ; Online: Hidradenitis Suppurativa

    S. Morteza Seyed Jafari / Robert E. Hunger / Christoph Schlapbach

    Frontiers in Medicine, Vol

    Current Understanding of Pathogenic Mechanisms and Suggestion for Treatment Algorithm

    2020  Volume 7

    Abstract: Hidradenitis suppurativa is one of the most distressing dermatological conditions and has a significant negative impact on patients' quality of life. However, the exact pathogenic mechanisms remain incompletely understood and—therefore—efficient ... ...

    Abstract Hidradenitis suppurativa is one of the most distressing dermatological conditions and has a significant negative impact on patients' quality of life. However, the exact pathogenic mechanisms remain incompletely understood and—therefore—efficient therapies are still lacking. The current manuscript focuses on new findings on its pathogenic mechanisms and aims to provide practical therapy recommendations.
    Keywords hidradenitis suppurativa ; pathomechanism ; pathogenesis ; therapy ; treatment ; Medicine (General) ; R5-920
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: PPAR-γ regulates the effector function of human T helper 9 cells by promoting glycolysis

    Nicole L. Bertschi / Oliver Steck / Fabian Luther / Cecilia Bazzini / Leonhard von Meyenn / Stefanie Schärli / Angela Vallone / Andrea Felser / Irene Keller / Olivier Friedli / Stefan Freigang / Nadja Begré / Susanne Radonjic-Hoesli / Cristina Lamos / Max Philip Gabutti / Michael Benzaquen / Markus Laimer / Dagmar Simon / Jean-Marc Nuoffer /
    Christoph Schlapbach

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 13

    Abstract: Abstract T helper 9 (TH9) cells promote allergic tissue inflammation and express the type 2 cytokines, IL-9 and IL-13, as well as the transcription factor, PPAR-γ. However, the functional role of PPAR-γ in human TH9 cells remains unknown. Here, we ... ...

    Abstract Abstract T helper 9 (TH9) cells promote allergic tissue inflammation and express the type 2 cytokines, IL-9 and IL-13, as well as the transcription factor, PPAR-γ. However, the functional role of PPAR-γ in human TH9 cells remains unknown. Here, we demonstrate that PPAR-γ drives activation-induced glycolysis, which, in turn, promotes the expression of IL-9, but not IL-13, in an mTORC1-dependent manner. In vitro and ex vivo experiments show that the PPAR-γ-mTORC1-IL-9 pathway is active in TH9 cells in human skin inflammation. Additionally, we find dynamic regulation of tissue glucose levels in acute allergic skin inflammation, suggesting that in situ glucose availability is linked to distinct immunological functions in vivo. Furthermore, paracrine IL-9 induces expression of the lactate transporter, MCT1, in TH cells and promotes their aerobic glycolysis and proliferative capacity. Altogether, our findings uncover a hitherto unknown relationship between PPAR-γ-dependent glucose metabolism and pathogenic effector functions in human TH9 cells.
    Keywords Science ; Q
    Subject code 570
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation

    Tom Hartwig / Pascale Zwicky / Bettina Schreiner / Nikhil Yawalkar / Phil Cheng / Alexander Navarini / Reinhard Dummer / Lukas Flatz / Curdin Conrad / Christoph Schlapbach / Burkhard Becher

    Cell Reports, Vol 25, Iss 13, Pp 3564-3572.e

    2018  Volume 4

    Abstract: Summary: Psoriasis is a chronic relapsing, remitting interleukin (IL)-23/IL-17-driven skin disease mediated by the interplay of T cells and polymorphonuclear granulocytes. Although preclinical studies have provided insights into the mechanisms of disease ...

    Abstract Summary: Psoriasis is a chronic relapsing, remitting interleukin (IL)-23/IL-17-driven skin disease mediated by the interplay of T cells and polymorphonuclear granulocytes. Although preclinical studies have provided insights into the mechanisms of disease initiation, the underpinnings of natural disease remission remain largely unknown. Here, we addressed the contribution of regulatory Foxp3+ T cells (Treg cells) in psoriasiform skin inflammation and remission using the Aldara-skin inflammation model in combination with the inducible depletion of Foxp3+ Treg cells. Loss of Treg cells exacerbated skin inflammation, but this did not involve increased γδ T cell expansion or the local production of the psoriasis-associated cytokines IL-17A, IL-17F, and IL-22, which are the main driving forces of disease development. Instead, Treg cells suppressed the infiltration of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing CD4+ T cells into the lesioned skin, and neutralizing GM-CSF in Treg cell-deficient mice reversed hyper-inflammation, resulting in disease regression. Therefore, we identified a non-redundant role of Treg cells restraining skin inflammation and mediating skin homeostasis. : The contribution of Treg cells to psoriasis is poorly understood. By combining inducible depletion of Treg cells with the Aldara model of psoriasiform inflammation, Hartwig et al. reveal a non-redundant role of Treg cells in promoting the remission of skin inflammation by limiting invasion of CD4+ GM-CSF-producing T cells into psoriatic skin. Keywords: psoriasis, melanoma, ipilimumab, Aldara, skin inflammation, Foxp3, Treg cells, CD4 T cells, GM-CSF
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2018-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: ABCB5 Identifies Immunoregulatory Dermal Cells

    Tobias Schatton / Jun Yang / Sonja Kleffel / Mayuko Uehara / Steven R. Barthel / Christoph Schlapbach / Qian Zhan / Stephen Dudeney / Hansgeorg Mueller / Nayoung Lee / Juliane C. de Vries / Barbara Meier / Seppe Vander Beken / Mark A. Kluth / Christoph Ganss / Arlene H. Sharpe / Ana Maria Waaga-Gasser / Mohamed H. Sayegh / Reza Abdi /
    Karin Scharffetter-Kochanek / George F. Murphy / Thomas S. Kupper / Natasha Y. Frank / Markus H. Frank

    Cell Reports, Vol 12, Iss 10, Pp 1564-

    2015  Volume 1574

    Abstract: Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP- ... ...

    Abstract Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5+ DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5+ DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2015-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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