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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Sconocchia, T; Hochgerner, M; Schwarzenberger, E; Tam-Amersdorfer, C; Borek, I; Benezeder, T; Bauer, T; Zyulina, V; Painsi, C; Passegger, C; Wolf, P; Sibilia, M; Strobl, H.
Bone morphogenetic protein signaling regulates skin inflammation via modulating dendritic cell function.
J Allergy Clin Immunol. 2021; 147(5):1810-1822
Doi: 10.1016/j.jaci.2020.09.038
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- Leading authors Med Uni Graz
- Sconocchia Tommaso
- Strobl Herbert
- Co-authors Med Uni Graz
- Bauer Thomas
- Benezeder Theresa Helena
- Borek Izabela Malgorzata
- Painsi Clemens
- Passegger Christina Angelika
- Schwarzenberger Elke
- Tam-Amersdorfer Carmen
- Wolf Peter
- Zyulina Victoria
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- Abstract:
- Bone morphogenetic proteins (BMPs) are members of the TGF-β family that signal via the BMP receptor (BMPR) signaling cascade, distinct from canonical TGF-β 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. We sought to investigate the role of BMP signaling in Treg-cell accumulation in psoriasis. 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-β signaling in DCs and Treg cells; and modeling of psoriatic skin inflammation in mice lacking the BMPR type 1a in CD11c+ cells. 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 that BMPR signaling licenses inflammation-associated Langerhans cell/DC to gain an enhanced capacity to promote Treg cells via BMPR-mediated CD25 induction and that this effect is associated with reduced skin inflammation. Psoriatic lesions are marked by constitutive high BMP7/BMPR signaling in keratinocytes, which instructs inflammatory DCs to gain enhanced Treg-cell-stimulatory activity. Locally secreted BMP7 can directly promote Treg-cell generation through the BMP signaling cascade. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (Keywords)
- Langerhans cells
- regulatory T cells
- monocyte-derived dendritic cell
- BMP7
- BMPR1a
- ALK3
- psoriasis