BMPR1a Is Required for the Optimal TGFβ1-Dependent CD207+ Langerhans Cell Differentiation and Limits Skin Inflammation through CD11c+ Cells.

The cytokine TGFβ1 induces epidermal Langerhans cell (LC) differentiation from human precursors, an effect mediated through BMPR1a/ALK3 signaling, as revealed from ectopic expression and receptor inhibition studies. Whether TGFβ1‒BMPR1a signaling is required for LC differentiation in vivo remained incompletely understood. We found that TGFβ1-deficient mice show defective perinatal expansion and differentiation of LCs. LCs can be identified within the normal healthy human epidermis by anti-BMPR1a immunohistology staining. Deletion of BMPR1a in all (vav+) hematopoietic cells revealed that BMPR1a is required for the efficient TGFβ1-dependent generation of CD207+ LC-like cells from CD11c+ intermediates in vitro. Similarly, BMPR1a was required for the optimal induction of CD207 by preformed major histocompatibility complex II‒positive epidermal resident LC precursors in the steady state. BMPR1a expression is strongly upregulated in epidermal cells in psoriatic lesions, and BMPR1aΔCD11c mice showed a defect in the resolution phase of allergic and psoriatic skin inflammation. Moreover, whereas LCs from these mice expressed CD207, BMPR1a counteracted LC activation and migration from skin explant cultures. Therefore, TGFβ1‒BMPR1a signaling seems to be required for the efficient induction of CD207 during LC differentiation in the steady state, and bone marrow‒derived lesional CD11c+ cells may limit established skin inflammation through enhanced BMPR1a signaling. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Mathias Hochgerner, Thomas Bauer, Victoria Zyulina, Elisabeth Glitzner, Sarah Warsi, Joanne E Konkel, Carmen Tam-Amersdorfer, Wanjun Chen, Stefan Karlsson, Maria Sibilia, Herbert Strobl. BMPR1a Is Required for the Optimal TGFβ1-Dependent CD207+ Langerhans Cell Differentiation and Limits Skin Inflammation through CD11c+ Cells. The Journal of investigative dermatology. 2022 Sep;142(9):2446-2454.e3

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PMID: 35300973

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