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

Hochgerner, Mathias LU ; Bauer, Thomas ; Zyulina, Victoria ; Glitzner, Elisabeth ; Warsi, Sarah LU ; Konkel, Joanne E. ; Tam-Amersdorfer, Carmen ; Chen, Wanjun ; Karlsson, Stefan LU orcid and Sibilia, Maria , et al. (2022) In Journal of Investigative Dermatology 142(9). p.3-2454
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 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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Investigative Dermatology
volume
142
issue
9
pages
3 - 2454
publisher
Elsevier
external identifiers
  • pmid:35300973
  • scopus:85135348845
ISSN
0022-202X
DOI
10.1016/j.jid.2022.02.014
language
English
LU publication?
yes
id
279007e5-97eb-4932-b234-9f6b270b57d8
date added to LUP
2022-10-28 14:08:31
date last changed
2024-06-13 20:29:47
@article{279007e5-97eb-4932-b234-9f6b270b57d8,
  abstract     = {{<p>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<sup>+</sup>) hematopoietic cells revealed that BMPR1a is required for the efficient TGFβ1-dependent generation of CD207<sup>+</sup> LC-like cells from CD11c<sup>+</sup> 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 BMPR1a<sup>ΔCD11c</sup> 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<sup>+</sup> cells may limit established skin inflammation through enhanced BMPR1a signaling.</p>}},
  author       = {{Hochgerner, Mathias and Bauer, Thomas and Zyulina, Victoria and Glitzner, Elisabeth and Warsi, Sarah and Konkel, Joanne E. and Tam-Amersdorfer, Carmen and Chen, Wanjun and Karlsson, Stefan and Sibilia, Maria and Strobl, Herbert}},
  issn         = {{0022-202X}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{3--2454}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Investigative Dermatology}},
  title        = {{BMPR1a Is Required for the Optimal TGFβ1-Dependent CD207<sup>+</sup> Langerhans Cell Differentiation and Limits Skin Inflammation through CD11c<sup>+</sup> Cells}},
  url          = {{http://dx.doi.org/10.1016/j.jid.2022.02.014}},
  doi          = {{10.1016/j.jid.2022.02.014}},
  volume       = {{142}},
  year         = {{2022}},
}