| First Author | Hochgerner M | Year | 2022 |
| Journal | J Invest Dermatol | Volume | 142 |
| Issue | 9 | Pages | 2446-2454.e3 |
| PubMed ID | 35300973 | Mgi Jnum | J:358894 |
| Mgi Id | MGI:7783813 | Doi | 10.1016/j.jid.2022.02.014 |
| Citation | Hochgerner M, et al. (2022) BMPR1a Is Required for the Optimal TGFbeta1-Dependent CD207(+) Langerhans Cell Differentiation and Limits Skin Inflammation through CD11c(+) Cells. J Invest Dermatol 142(9):2446-2454.e3 |
| abstractText | The cytokine TGFbeta1 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 TGFbeta1BMPR1a signaling is required for LC differentiation in vivo remained incompletely understood. We found that TGFbeta1-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 TGFbeta1-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 IIpositive epidermal resident LC precursors in the steady state. BMPR1a expression is strongly upregulated in epidermal cells in psoriatic lesions, and BMPR1a(DeltaCD11c) 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, TGFbeta1BMPR1a signaling seems to be required for the efficient induction of CD207 during LC differentiation in the steady state, and bone marrowderived lesional CD11c(+) cells may limit established skin inflammation through enhanced BMPR1a signaling. |
