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. 2018 Jan;19(1):63-75.
doi: 10.1038/s41590-017-0012-z. Epub 2017 Dec 4.

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

Solana G Alculumbre  1   2 , Violaine Saint-André  1   3 , Jeremy Di Domizio  4 , Pablo Vargas  1   5 , Philemon Sirven  1   2 , Pierre Bost  1   2   6 , Mathieu Maurin  1   2 , Paolo Maiuri  1   7 , Maxime Wery  1   3 , Mabel San Roman  1   2 , Léa Savey  8   9 , Maxime Touzot  10 , Benjamin Terrier  11 , David Saadoun  8   9 , Curdin Conrad  4 , Michel Gilliet  4 , Antonin Morillon  1   3 , Vassili Soumelis  12   13   14
Affiliations

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

Solana G Alculumbre et al. Nat Immunol. 2018 Jan.

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.

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