Diversification of human plasmacytoid predendritic cells in response to a single stimulus.
Solana G AlculumbreViolaine Saint-AndréJeremy Di DomizioPablo VargasPhilemon SirvenPierre BostMathieu MaurinPaolo MaiuriMaxime WeryMabel San RomanLéa SaveyMaxime TouzotBenjamin TerrierDavid SaadounCurdin ConradMichel GillietAntonin MorillonVassili SoumelisPublished in: Nature immunology (2017)
Innate immune cells adjust to microbial and inflammatory stimuli through a process termed environmental plasticity, which links a given individual stimulus to a unique activated state. Here, we report that activation of human plasmacytoid predendritic cells (pDCs) with a single microbial or cytokine stimulus triggers cell diversification into three stable subpopulations (P1-P3). P1-pDCs (PD-L1+CD80-) displayed a plasmacytoid morphology and specialization for type I interferon production. P3-pDCs (PD-L1-CD80+) adopted a dendritic morphology and adaptive immune functions. P2-pDCs (PD-L1+CD80+) displayed both innate and adaptive functions. Each subpopulation expressed a specific coding- and long-noncoding-RNA signature and was stable after secondary stimulation. P1-pDCs were detected in samples from patients with lupus or psoriasis. pDC diversification was independent of cell divisions or preexisting heterogeneity within steady-state pDCs but was controlled by a TNF autocrine and/or paracrine communication loop. Our findings reveal a novel mechanism for diversity and division of labor in innate immune cells.
Keyphrases
- dendritic cells
- immune response
- single cell
- induced apoptosis
- long noncoding rna
- endothelial cells
- cell cycle arrest
- microbial community
- cell therapy
- systemic lupus erythematosus
- induced pluripotent stem cells
- rheumatoid arthritis
- endoplasmic reticulum stress
- nk cells
- genome wide
- pluripotent stem cells
- stem cells
- disease activity
- mesenchymal stem cells
- bone marrow
- signaling pathway
- cell death
- dna methylation
- human health
- life cycle