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SHR Neuro Krebs Kardio Lipid

Borek, I; Köffel, R; Feichtinger, J; Spies, M; Glitzner-Zeis, E; Hochgerner, M; Sconocchia, T; Krump, C; Tam-Amersdorfer, C; Passegger, C; Benezeder, T; Tittes, J; Redl, A; Painsi, C; Thallinger, GG; Wolf, P; Stary, G; Sibilia, M; Strobl, H.
BMP7 aberrantly induced in the psoriatic epidermis instructs inflammation-associated Langerhans cells.
J Allergy Clin Immunol. 2020; 145(4):1194-1207
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Benezeder Theresa Helena
Borek Izabela Malgorzata
Feichtinger Julia
Köffel René
Krump Corinna
Painsi Clemens
Passegger Christina Angelika
Sconocchia Tommaso
Strobl Herbert
Tam-Amersdorfer Carmen
Wolf Peter
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Abstract:
Epidermal hyperplasia represents a morphologic hallmark of psoriatic skin lesions. Langerhans cells (LCs) in the psoriatic epidermis engage with keratinocytes (KCs) in tight physical interactions; moreover, they induce T-cell-mediated immune responses critical to psoriasis. This study sought to improve the understanding of epidermal factors in psoriasis pathogenesis. BMP7-LCs versus TGF-β1-LCs were phenotypically characterized and their functional properties were analyzed using flow cytometry, cell kinetic studies, co-culture with CD4 T cells, and cytokine measurements. Furthermore, immunohistology of healthy and psoriatic skin was performed. Additionally, in vivo experiments with Junf/fJunBf/fK5cre-ERT mice were carried out to assess the role of bone morphogenetic protein (BMP) signaling in psoriatic skin inflammation. This study identified a KC-derived signal (ie, BMP signaling) to promote epidermal changes in psoriasis. Whereas BMP7 is strictly confined to the basal KC layer in the healthy skin, it is expressed at high levels throughout the lesional psoriatic epidermis. BMP7 instructs precursor cells to differentiate into LCs that phenotypically resemble psoriatic LCs. These BMP7-LCs exhibit proliferative activity and increased sensitivity to bacterial stimulation. Moreover, aberrant high BMP signaling in the lesional epidermis is mediated by a KC intrinsic mechanism, as suggested from murine data and clinical outcome after topical antipsoriatic treatment in human patients. These data indicate that available TGF-β family members within the lesional psoriatic epidermis preferentially signal through the canonical BMP signaling cascade to instruct inflammatory-type LCs and to promote psoriatic epidermal changes. Targeting BMP signaling might allow to therapeutically interfere with cutaneous psoriatic manifestations. Copyright © 2020. Published by Elsevier Inc.

Find related publications in this database (Keywords)
BMP7
Langerhans cells
psoriasis
TGF-beta signaling
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