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

Borek, Izabela; Köffel, René; Feichtinger, Julia; Spies, Melanie; Glitzner, Elisabeth; Hochgerner, Markus; Sconocchia, Tommaso; Krump, Corinna; Tam‐Amersdorfer, Carmen; Passegger, Christina; Benezeder, Theresa; Tittes, Julia; Redl, Anna; Painsi, Clemens; Thallinger, Gerhard; Wolf, Peter; Stary, Georg; Sibilia, Maria; Strobl, Herbert

doi:10.1016/j.jaci.2019.12.011

Cited by 16 publications

(35 citation statements)

References 74 publications

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“…Surface marker staining was performed as previously described. 11 FoxP3 expression was detected using the FoxP3 staining buffer set (ThermoFisher, Waltham, Mass). Intracellular cytokines were detected using the FIX&PERM kit (Nordic MUbio, Susteren, the Netherlands).…”

Section: Flow Cytometrymentioning

confidence: 99%

“…We recently described that the lesional psoriatic epidermis is marked by aberrant high BMP7 expression and concomitant downstream activation of BMP signaling. 11 To study a possible functional interrelationship between BMP7 and Treg cells, we performed a side-by-side quantification of BMP7 expression intensity and Treg-cell numbers in psoriatic lesions and compared these with uninvolved skin from the same patients. BMP7 expression in the nonlesional skin is limited to the epidermis where it is confined to the basal KC layer (Fig 1…”

Section: Bmp7 Expression Intensity Is Positively Associated With Numbmentioning

confidence: 99%

“…BMP7 can replace TGF-b1 in inducing LC generation from CD34 1 cells, and the generated LCs resemble lesional psoriatic LCs (CD206 1 CD1c 1 TLR2 1 ). 11,25 Consistent with their higher expression intensity of TLR2, mimicking lesional LCs, 11 in vitro generated BMP7-LCs produce higher levels of cytokines in response to microbial stimulation than do TGF-b1-LCs. 25 However, the function of these cells remained unclear.…”

mentioning

confidence: 94%

“…16 Consistently, we observed that BMP7 is aberrantly expressed throughout the lesional psoriatic epidermis both in human patients and in murine psoriasis models; for comparison, BMP7 is restricted to basal keratinocytes (KCs) in the steady state. 11 In contrast to BMP signaling, components of canonical TGF-b signaling were repressed in psoriatic skin lesions. [17][18][19] Although both pro-and anti-inflammatory roles of BMP signaling have been described, [20][21][22][23][24] its function in epidermal homeostasis remains poorly understood.…”

mentioning

confidence: 97%

“…7,8 The lesional human psoriatic epidermis contains in addition to steady-state-like LCs a second population of epidermal CD206 1 CD1c 1 LC-like dendritic cells (DCs). [9][10][11] These cells are neorecruited to lesions and seem to arise from circulating precursors, given that approximately 40% of murine lesional LC-like cells in a psoriasis model are derived from the bone marrow. 12 Murine LC depletion experiments showed that LCs limit psoriatic inflammation but are dispensable for the onset of inflammatory lesions, 12,13 compatible with a possible negative regulatory function of inflammatory LCs.…”

mentioning

confidence: 99%

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Bone morphogenetic protein signaling regulates skin inflammation via modulating dendritic cell function

Sconocchia

Hochgerner

Schwarzenberger

et al. 2021

Journal of Allergy and Clinical Immunology

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Background: Bone morphogenetic proteins (BMPs) are members of the TGF-b family that signal via the BMP receptor (BMPR) signaling cascade, distinct from canonical TGF-b signaling. BMP downstream signaling is strongly induced within epidermal keratinocytes in cutaneous psoriatic lesions, and BMP7 instructs monocytic cells to acquire characteristics of psoriasis-associated Langerhans dendritic cells (DCs). Regulatory T (Treg)-cell numbers strongly increase during psoriatic skin inflammation and were recently shown to limit psoriatic skin inflammation. However, the factors mediating Treg-cell accumulation in psoriatic skin currently remain unknown. Objective: We sought to investigate the role of BMP signaling in Treg-cell accumulation in psoriasis. Methods: The following methods were used: immunohistology of patients and healthy controls; ex vivo models of Treg-cell generation in the presence or absence of Langerhans cells; analysis of BMP versus canonical TGF-b signaling in DCs and Treg cells; and modeling of psoriatic skin inflammation in mice lacking the BMPR type 1a in CD11c 1 cells. Results: We here demonstrated a positive correlation between Treg-cell numbers and epidermal BMP7 expression in cutaneous psoriatic lesions and show that unlike Treg cells from healthy skin, a portion of inflammation-associated Treg cells exhibit constitutive-active BMP signaling. We further found

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Section: Flow Cytometrymentioning

confidence: 99%

Section: Bmp7 Expression Intensity Is Positively Associated With Numbmentioning

confidence: 99%

mentioning

confidence: 94%

mentioning

confidence: 97%

mentioning

confidence: 99%

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Bone morphogenetic protein signaling regulates skin inflammation via modulating dendritic cell function

Sconocchia

Hochgerner

Schwarzenberger

et al. 2021

Journal of Allergy and Clinical Immunology

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The Immunology of Psoriasis—Current Concepts in Pathogenesis

Sieminska,

Pieniawska,

Grzywa

2024

Clinic Rev Allerg Immunol

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Psoriasis is one of the most common inflammatory skin diseases with a chronic, relapsing-remitting course. The last decades of intense research uncovered a pathological network of interactions between immune cells and other types of cells in the pathogenesis of psoriasis. Emerging evidence indicates that dendritic cells, TH17 cells, and keratinocytes constitute a pathogenic triad in psoriasis. Dendritic cells produce TNF-α and IL-23 to promote T cell differentiation toward TH17 cells that produce key psoriatic cytokines IL-17, IFN-γ, and IL-22. Their activity results in skin inflammation and activation and hyperproliferation of keratinocytes. In addition, other cells and signaling pathways are implicated in the pathogenesis of psoriasis, including TH9 cells, TH22 cells, CD8+ cytotoxic cells, neutrophils, γδ T cells, and cytokines and chemokines secreted by them. New insights from high-throughput analysis of lesional skin identified novel signaling pathways and cell populations involved in the pathogenesis. These studies not only expanded our knowledge about the mechanisms of immune response and the pathogenesis of psoriasis but also resulted in a revolution in the clinical management of patients with psoriasis. Thus, understanding the mechanisms of immune response in psoriatic inflammation is crucial for further studies, the development of novel therapeutic strategies, and the clinical management of psoriasis patients. The aim of the review was to comprehensively present the dysregulation of immune response in psoriasis with an emphasis on recent findings. Here, we described the role of immune cells, including T cells, B cells, dendritic cells, neutrophils, monocytes, mast cells, and innate lymphoid cells (ILCs), as well as non-immune cells, including keratinocytes, fibroblasts, endothelial cells, and platelets in the initiation, development, and progression of psoriasis.

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Meeting Report of the 16th International Langerhans Cell Workshop: Recent Developments in Langerhans Cell and Skin Dendritic Cell Biology and their Therapeutic Application

Clausen

Romani

Stoitzner

2020

Journal of Investigative Dermatology

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

Cited by 16 publications

References 74 publications

Bone morphogenetic protein signaling regulates skin inflammation via modulating dendritic cell function

Bone morphogenetic protein signaling regulates skin inflammation via modulating dendritic cell function

The Immunology of Psoriasis—Current Concepts in Pathogenesis

Meeting Report of the 16th International Langerhans Cell Workshop: Recent Developments in Langerhans Cell and Skin Dendritic Cell Biology and their Therapeutic Application

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