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

Area of Science:

• Immunodermatology
• Molecular signaling pathways
• Autoimmune disease mechanisms

Background:

• Psoriatic skin lesions exhibit increased Bone Morphogenetic Protein (BMP) signaling in keratinocytes.
• BMP7 influences monocytic cells to develop into Langerhans dendritic cells (DCs) characteristic of psoriasis.
• Regulatory T (Treg) cells increase in psoriatic inflammation and limit disease severity, but the drivers of their accumulation are unknown.

Purpose of the Study:

• To investigate the role of BMP signaling in the accumulation of Treg cells within psoriatic skin.

Main Methods:

• Immunohistology on patient and control skin samples.
• Ex vivo Treg cell generation assays with and without Langerhans cells.
• Analysis of BMP and TGF-β signaling in DCs and Treg cells.
• Murine model of psoriasis using CD11c-specific BMPR1a knockout.

Main Results:

• A positive correlation was observed between Treg cell numbers and epidermal BMP7 expression in psoriatic lesions.
• Inflammation-associated Treg cells displayed constitutive BMP signaling, unlike those from healthy skin.
• BMPR signaling in Langerhans cells/DCs enhanced their capacity to promote Treg cells via CD25 induction, correlating with reduced skin inflammation.

Conclusions:

• Psoriatic lesions show high BMP7/BMPR signaling in keratinocytes, which enhances inflammatory DC activity for Treg cell stimulation.
• Locally secreted BMP7 directly promotes Treg cell generation through the BMP signaling pathway.