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Nat Immunol. 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.

Author information

1
Institut Curie, Centre de Recherche, PSL Research University, Paris, France.
2
INSERM U932, Immunity and Cancer, Paris, France.
3
CNRS UMR 3244, ncRNA, Epigenetic, and Genome Fluidity, Université Pierre et Marie Curie, Paris, France.
4
Department of Dermatology, University Hospital CHUV, Lausanne, Switzerland.
5
CNRS UMR144, Paris, France.
6
Department of Biology, Ecole Normale Supérieure, PSL Research University, Paris, France.
7
IFOM Foundation, Institute FIRC of Molecular Oncology, Milan, Italy.
8
UMR7211 and Inflammation-Immunopathology-Biotherapy Departement (DHU i2B), Sorbonne Universités, UPMC Université de Paris, Paris, France.
9
Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié Salpétrière, Department of Internal Medicine and Clinical Immunology, National Reference Center for Autoimmune and Systemic Diseases, Paris, France.
10
AURA Paris Plaisance, Paris, France.
11
Department of Internal Medicine, National Referral Center for Rare Autoimmune and Systemic Diseases, Cochin Hospital, AP-HP, Université Paris Descartes, Paris, France.
12
Institut Curie, Centre de Recherche, PSL Research University, Paris, France. vassili.soumelis@curie.fr.
13
INSERM U932, Immunity and Cancer, Paris, France. vassili.soumelis@curie.fr.
14
CIC IGR-Curie 1428, Paris, France. vassili.soumelis@curie.fr.

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.

PMID:
29203862
DOI:
10.1038/s41590-017-0012-z
[Indexed for MEDLINE]

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