Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Lang, M; Krump, C; Meshcheryakova, A; Tam-Amersdorfer, C; Schwarzenberger, E; Passegger, C; Connolly, S; Mechtcheriakova, D; Strobl, H.
Microenvironmental and cell intrinsic factors governing human cDC2 differentiation and monocyte reprogramming.
FRONT IMMUNOL. 2023; 14: 1216352
Doi: 10.3389/fimmu.2023.1216352
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Lang Magdalena
- Strobl Herbert
- Co-Autor*innen der Med Uni Graz
- Connolly Sally
- Krump Corinna
- Passegger Christina Angelika
- Schwarzenberger Elke
- Tam-Amersdorfer Carmen
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- cDC2s occur abundantly in peripheral tissues and arise from circulating blood cDC2s. However, the factors governing cDC2 differentiation in tissues, especially under inflammatory conditions, remained poorly defined. We here found that psoriatic cDC2s express the efferocytosis receptor Axl and exhibit a bone morphogenetic protein (BMP) and p38MAPK signaling signature. BMP7, strongly expressed within the lesional psoriatic epidermis, cooperates with canonical TGF-β1 signaling for inducing Axl+cDC2s from blood cDC2s in vitro. Moreover, downstream induced p38MAPK promotes Axl+cDC2s at the expense of Axl+CD207+ Langerhans cell differentiation from blood cDC2s. BMP7 supplementation allowed to model cDC2 generation and their further differentiation into LCs from CD34+ hematopoietic progenitor cells in defined serum-free medium. Additionally, p38MAPK promoted the generation of another cDC2 subset lacking Axl but expressing the non-classical NFkB transcription factor RelB in vitro. Such RelB+cDC2s occurred predominantly at dermal sites in the inflamed skin. Finally, we found that cDC2s can be induced to acquire high levels of the monocyte lineage identity factor kruppel-like-factor-4 (KLF4) along with monocyte-derived DC and macrophage phenotypic characteristics in vitro. In conclusion, inflammatory and psoriatic epidermal signals instruct blood cDC2s to acquire phenotypic characteristics of several tissue-resident cell subsets.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Monocytes - metabolism
- Dendritic Cells - metabolism
- Cell Differentiation - administration & dosage
- Skin - administration & dosage
- Epidermis - metabolism
- Find related publications in this database (Keywords)
- dendritic cell
- Langerhans cell
- transcriptional reprogramming
- lineage decision
- epidermal signaling
- inflammatory skin disease