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.
Diversification of human plasmacytoid predendritic cells in response to a single stimulus / Alculumbre, S.g., Saint-Andre, V., Di Domizio, J., Vargas, P., Sirven, P., Bost, P., Maurin, M., Maiuri, P., Wery, M., San Roman, M., Savey, L., Touzot, M., Terrier, B., Saadoun, D., Conrad, C., Gilliet, M., Morillon, A., Soumelis, V.. - In: NATURE IMMUNOLOGY. - ISSN 1529-2908. - 19:1(2018), pp. 63-+. [10.1038/s41590-017-0012-z]
Diversification of human plasmacytoid predendritic cells in response to a single stimulus
Maiuri P;
2018
Abstract
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.| File | Dimensione | Formato | |
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Alculumbre et al. - 2018 - Diversification of human plasmacytoid predendritic cells in response to a single stimulus article.pdf
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