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

Authors :
Hochgerner, Mathias
Bauer, Thomas
Zyulina, Victoria
Glitzner, Elisabeth
Warsi, Sarah
Konkel, Joanne E.
Tam-Amersdorfer, Carmen
Chen, Wanjun
Karlsson, Stefan
Sibilia, Maria
Strobl, Herbert
Source :
Journal of Investigative Dermatology; September 2022, Vol. 142 Issue: 9 p2446-2454.e3
Publication Year :
2022

Abstract

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 BMPR1ain 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 BMPR1aΔCD11cmice 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.

Details

Language :
English
ISSN :
0022202X and 15231747
Volume :
142
Issue :
9
Database :
Supplemental Index
Journal :
Journal of Investigative Dermatology
Publication Type :
Periodical
Accession number :
ejs59155384
Full Text :
https://doi.org/10.1016/j.jid.2022.02.014