Diversification of human plasmacytoid predendritic cells in response to a single stimulus
2 DIG CANCER - Dynamique de l'information génétique : bases fondamentales et cancer
3 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
4 Biologie Cellulaire et Cancer
5 ENS-PSL - École normale supérieure - Paris
6 PSL - Université Paris Sciences et Lettres
7 Institut Curie [Paris]
8 IFOM - IFOM, Istituto FIRC di Oncologia Molecolare
9 DIG CANCER - Dynamique de l'information génétique : bases fondamentales et cancer
10 CHU Pitié-Salpêtrière [AP-HP]
11 AURA Paris - Plaisance
12 Centre National de Référence Maladies Systémiques et Autoimmunes Rares
13 I3 - Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière]
14 CIC1428 IGR-CURIE
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- ORCID : 0000-0002-2162-0909
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- IdHAL : pvargas
- ORCID : 0000-0002-6475-494X
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- ORCID : 0000-0002-1989-1304
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- ORCID : 0000-0003-3628-9996
- IdRef : 119038765
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- IdHAL : antonin-morillon
- ORCID : 0000-0002-0575-5264
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Résumé
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.