Diversification of human plasmacytoid predendritic cells in response to a single stimulus

• Published in: Nature immunology Vol. 19; no. 1; pp. 63 - 75
• Main Authors: Alculumbre, Solana G., Saint-André, Violaine, Di Domizio, Jeremy, Vargas, Pablo, Sirven, Philemon, Bost, Pierre, Maurin, Mathieu, Maiuri, Paolo, Wery, Maxime, Roman, Mabel San, Savey, Léa, Touzot, Maxime, Terrier, Benjamin, Saadoun, David, Conrad, Curdin, Gilliet, Michel, Morillon, Antonin, Soumelis, Vassili
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2018; Nature Publishing Group
• Subjects: Adaptive Immunity - immunology; Autocrine signalling; B7-1 Antigen - immunology; B7-1 Antigen - metabolism; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; Biodiversity; Biological response modifiers; Biomedical and Life Sciences; Biomedicine; CD80 antigen; Cells, Cultured; Cytokines - genetics; Cytokines - immunology; Cytokines - metabolism; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - ultrastructure; Diversification; Division of labor; Gene Expression - immunology; Gene Expression Profiling - methods; Heterogeneity; Humans; Immunity, Innate - immunology; Immunology; Infectious Diseases; Inflammation; Innate immunity; Interferon; Interferon Type I - genetics; Interferon Type I - immunology; Interferon Type I - metabolism; Life Sciences; Lupus; Lupus Erythematosus, Systemic - immunology; Microscopy, Electron, Transmission; Morphology; Orthomyxoviridae - immunology; Paracrine signalling; PD-L1 protein; Psoriasis; Psoriasis - immunology; Ribonucleic acid; RNA; Skin diseases; Specialization; Subpopulations; Tumor necrosis factor
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/s41590-017-0012-z

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. Plasmacytoid dendritic cells (pDCs) are known for their copious IFN-I production. Soumelis and colleagues show that functionally and transcriptomically distinct human pDC populations can be generated from a single microbial or cytokine stimulus.