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J Allergy Clin Immunol. 2019 Dec 20. pii: S0091-6749(19)31713-0. doi: 10.1016/j.jaci.2019.12.011. [Epub ahead of print]

BMP7 aberrantly induced in the psoriatic epidermis instructs inflammation-associated Langerhans cells.

Author information

1
Otto Loewi Research Center, Chair of Immunology and Pathophysiology, Medical University of Graz, Austria.
2
Institute of Anatomy, University of Bern, Switzerland.
3
Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Austria.
4
Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna, Austria.
5
Department of Dermatology, Medical University of Graz, Austria.
6
Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Austria.
7
Department of Dermatology, State Hospital Klagenfurt, Austria.
8
Institute of Computational Biotechnology, Graz University of Technology, Austria; OMICS Center Graz, BioTechMed Graz, Austria.
9
Otto Loewi Research Center, Chair of Immunology and Pathophysiology, Medical University of Graz, Austria. Electronic address: herbert.strobl@medunigraz.at.

Abstract

BACKGROUND:

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.

OBJECTIVE:

Epidermal factors in psoriasis pathogenesis remain poorly understood.

METHODS:

We phenotypically characterized BMP7-LCs vs. TGF-β1-LCs and analyzed their functional properties 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/fK5creER mice were carried out to assess the role of BMP signaling in psoriatic skin inflammation.

RESULTS:

Here we identified a KC-derived signal, i.e. bone morphogenetic protein (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 anti-psoriatic treatment in human patients.

CONCLUSION:

Our 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.

KEYWORDS:

BMP7; Langerhans cells; Psoriasis; TGF-β signaling

PMID:
31870764
DOI:
10.1016/j.jaci.2019.12.011

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