Nonplasmacytoid, High IFN-α–Producing, Bone Marrow Dendritic Cells

O’Keeffe, Meredith; Fancke, Ben; Suter, Mark; Ramm, Georg; Clark, J. M.; Wu, Li; Hochrein, Hubertus

doi:10.4049/jimmunol.1101365

Cited by 12 publications

(6 citation statements)

References 44 publications

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“…The strongest correlation with chemokine expression was the expression of CCR9, which was highest on the BFP − pDC population. Although CCR9 expression in BM pDCs is a marker of heterogeneity, others have proposed that, alternatively, these cells are precursors of cDCs . In our hands, the BFP + pDCs are largely CCR9 − and have higher expression of PU.1, similar to cDC precursors.…”

Section: Discussionsupporting

confidence: 43%

Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation

et al. 2018

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Plasmacytoid dendritic cells (pDCs) play a critical role in bridging the innate and adaptive immune systems. pDCs are specialized type I interferon (IFN) producers, which has implicated them as initiators of autoimmune pathogenesis. However, little is known about the downstream effectors of type I IFN signaling that amplify autoimmune responses. Here, we have used a chemokine reporter mouse to determine the CXCR3 ligand responses in DCs subsets. Following TLR7 stimulation, conventional type 1 and type 2 DCs (cDC1 and cDC2, respectively) uniformly upregulate CXCL10. By contrast, the proportion of chemokine positive pDCs was significantly less, and stable CXCL10 and CXCL10 populations could be distinguished. CXCL9 expression was induced in all cDC1s, in half of the cDC2 but not by pDCs. The requirement for IFNAR signaling for chemokine reporter expression was interrogated by receptor blocking and deficiency and shown to be critical for CXCR3 ligand expression in Flt3-ligand-derived DCs. Chemokine-producing potential was not concordant with the previously identified markers of pDC heterogeneity. Finally, we show that CXCL10 and CXCL10 populations are transcriptionally distinct, expressing unique transcriptional regulators, IFN signaling molecules, chemokines, cytokines, and cell surface markers. This work highlights CXCL10 as a downstream effector of type I IFN signaling and suggests a division of labor in pDCs subtypes that likely impacts their function as effectors of viral responses and as drivers of inflammation.

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Section: Discussionsupporting

confidence: 43%

Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation

et al. 2018

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“…Alternatively IFN may be secreted by cells such as DCs in response to ASFV infection. Many types of DCs can secrete IFN in response to viral infection ( O’Keeffe et al, 2012 , Schulte et al, 2015 ) and pDCs in particular secrete large quantities of IFN in response to viral infection. A population of PBMCs enriched for CD4 + /CD172 + cells produced large quantities of IFN when exposed to both virulent and low virulent ASFV.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity of African swine fever virus to type I interferon is linked to genes within multigene families 360 and 505

et al. 2016

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African swine fever virus (ASFV) causes a lethal haemorrhagic disease of pigs. There are conflicting reports on the role of interferon in ASFV infection. We therefore analysed the interaction of ASFV with porcine interferon, in vivo and in vitro. Virulent ASFV induced biologically active IFN in the circulation of pigs from day 3-post infection, whereas low virulent OUR T88/3, which lacks genes from multigene family (MGF) 360 and MGF505, did not. Infection of porcine leucocytes enriched for dendritic cells, with ASFV, in vitro, induced high levels of interferon, suggesting a potential source of interferon in animals undergoing acute ASF. Replication of OUR T88/3, but not virulent viruses, was reduced in interferon pretreated macrophages and a recombinant virus lacking similar genes to those absent in OUR T88/3 was also inhibited. These findings suggest that as well as inhibiting the induction of interferon, MGF360 and MGF505 genes also enable ASFV to overcome the antiviral state.

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“…Two pDC subsets have been defined by CD9 expression 219 . The CD9 + subset has high type I IFN producing and T cell stimulatory capacities and may partially overlap with the nonplasmacytoid, high type I IFN producing DC subset described in the bone marrow 220 and CCR9 − pDC-like common DC precursors.…”

Section: Phenotypes Of Human and Mouse Pdcsmentioning

confidence: 99%

The multifaceted biology of plasmacytoid dendritic cells

2015

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Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset that specializes in the production of type I interferons (IFNs). pDCs promote antiviral immune responses and have been implicated in the pathogenesis of autoimmune diseases characterized by a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. Here, we review recent progress from the field of pDC biology, focusing on: the molecular mechanisms that regulate pDC development and functions; the pathways involved in their sensing of pathogens and endogenous nucleic acids; the function of pDCs at mucosal sites; and their roles in infections, autoimmunity and cancer.

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Nonplasmacytoid, High IFN-α–Producing, Bone Marrow Dendritic Cells

Cited by 12 publications

References 44 publications

Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation

Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation

Sensitivity of African swine fever virus to type I interferon is linked to genes within multigene families 360 and 505

The multifaceted biology of plasmacytoid dendritic cells

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