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

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-L1CD80) displayed a plasmacytoid morphology and specialization for type I interferon production. P3-pDCs (PD-L1CD80) adopted a dendritic morphology and adaptive immune functions. P2-pDCs (PD-L1CD80) 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.

Targeting human Plasmacytoid dendritic cells through BDCA2 prevents inflammation and fibrosis in xenotransplant mouse model of Scleroderma

“…3C and STab.2). CD274 expression was ODN-induced and dependent on BDCA2 targeting, which supported ours and others' observations that 12-18 h TLR stimulation induces P1 and P2 subsets that are CD274 + and secrete IFN [25]. ODN-induced IL6 expression was also dependent on BDCA2 targeting.…”

“…2B-C). Similarly, to what has been observed following viral stimulation [25], treatment with ODN induced pDC to differentiate in the specific subtypes, with 62% of pDC differentiating in P1 and P2 ( Fig. 2B-C).…”

“…It has been recently shown that TLR-induced activation of pDC triggers stable cell differentiation into three stable sub-types, with PD-L1(CD274) + CD80 -(P1) and PD-L1(CD274) + CD80 + (P2) subpopulations specialized in type I IFN production both in healthy controls and patients with autoimmune conditions [25].…”

Integrated Cross-Species Analysis Identifies a Conserved Transitional Dendritic Cell Population

“…Indeed, pDCs are known to lose IFN-I production potential and increase antigen presentation capacity during stimulation (Palucka et al, 2005), which are characteristics associated with tDCs. This pDC conversion, also called plasticity, has been observed for both human and mouse pDCs (Alcá ntara-Herná ndez et al, Alculumbre et al, 2018;Grouard et al, 1997;Liou et al, 2008;Manh et al, 2013). The identification of mouse and human tDCs creates an opportunity to explore pDC plasticity in vivo.…”

Whole‐genome analysis uncovers recurrent IKZF1 inactivation and aberrant cell adhesion in blastic plasmacytoid dendritic cell neoplasm

“…BPDCN samples were compared to a control group formed by resting pDCs. RNA‐seq data of pDC controls were generated by Alculumbre et al and downloaded from GEO (https://www.ncbi.nlm.nih.gov/geo/; GSE84204) . Genes with a FDR < 0.01 were considered differentially expressed (DE).…”