Bone morphogenetic protein signaling regulates skin inflammation via modulating dendritic cell function - 05/05/21
Abstract |
Background |
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.
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-β signaling in DCs and Treg cells; and modeling of psoriatic skin inflammation in mice lacking the BMPR type 1a in CD11c+ 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 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.
Conclusions |
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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Langerhans cells, regulatory T cells, monocyte-derived dendritic cell, BMP7, BMPR1a, ALK3, psoriasis
Abbreviations used : BMP, BMPR, DC, KC, LC, moDC, TGFβR1, Treg, WT
Plan
| This work was supported by the Austrian Science Fund (FWF; grant no. W1241 to H.S.) and the Medical University of Graz through the PhD program in Molecular Fundamentals of Inflammation (DK-MOLIN). Additional funding was provided through the Austrian Science Fund (FWF; grant no.W1212 to H.S.) and the Medical University of Vienna through the PhD program Inflammation and Immunity, and by the BioTechMed Graz (project “secretome” to H.S.). |
|
| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 5
P. 1810 - mai 2021 Retour au numéro
Article précédent
- Treatment of granuloma annulare and suppression of proinflammatory cytokine activity with tofacitinib
- Alice Wang, Nur-Taz Rahman, Meaghan K. McGeary, Michael Murphy, Austin McHenry, Danielle Peterson, Marcus Bosenberg, Richard A. Flavell, Brett King, William Damsky
- Infant pacifier sanitization and risk of challenge-proven food allergy: A cohort study
- Victoria X. Soriano, Jennifer J. Koplin, Mike Forrester, Rachel L. Peters, Martin O’Hely, Shyamali C. Dharmage, Rosemary Wright, Sarath Ranganathan, David Burgner, Kristie Thompson, Terence Dwyer, Peter Vuillerman, Anne-Louise Ponsonby, BIS Investigator Group
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?