Cutting Edge: IFN-β Expression in the Spleen Is Restricted to a Subpopulation of Plasmacytoid Dendritic Cells Exhibiting a Specific Immune Modulatory Transcriptome Signature

Abstract

Type I IFNs are critical in initiating protective antiviral immune responses, and plasmacytoid dendritic cells (pDCs) represent a major source of these cytokines. We show that only few pDCs are capable of producing IFN-β after virus infection or CpG stimulation. Using IFNβ/YFP reporter mice, we identify these IFN-β–producing cells in the spleen as a CCR9+CD9− pDC subset that is localized exclusively within the T/B cell zones. IFN-β–producing pDCs exhibit a distinct transcriptome profile, with higher expression of genes encoding cytokines and chemokines, facilitating T cell recruitment and activation. These distinctive characteristics of IFN-β–producing pDCs are independent of the type I IFNR-mediated feedback loop. Furthermore, IFN-β–producing pDCs exhibit enhanced CCR7-dependent migratory properties in vitro. Additionally, they effectively recruit T cells in vivo in a peritoneal inflammation model. We define “professional type I IFN-producing cells” as a distinct subset of pDCs specialized in coordinating cellular immune responses.

In Vivo Conditions Enable IFNAR-Independent Type I Interferon Production by Peritoneal CD11b + Cells upon Thogoto Virus Infection

“…Along this line, Bauer et al recently showed that upon treatment of IFN-␤ mob/mob mice with CpG, a stimulus for pDC but not mDC or PEC to produce type I IFNs (Fig. 1B), only a minor and distinct population of pDC within the spleen was stimulated to express the YFP reporter gene (48).…”

Homeostatic control of dendritic cell numbers and differentiation

“…In contrast to cDCs, pDCs exhibit an endosomal localization of TLR7 and TLR9 and a constitutive high expression of IRF7, which enables them to respond rapidly to viruses, bacteria or self‐nucleic acids . Specifically, due to their unique high expression of IRF7, pDCs are capable of producing large amounts of type I interferon and proinflammatory cytokines, immediately in response to stimulation . Furthermore, cytokines secreted by activated pDCs attract T cells and put them in close contact with DCs .…”

“…Specifically, due to their unique high expression of IRF7, pDCs are capable of producing large amounts of type I interferon and proinflammatory cytokines, immediately in response to stimulation . Furthermore, cytokines secreted by activated pDCs attract T cells and put them in close contact with DCs . Brewitz et al .…”

“…This mechanism creates a confined microenvironment for efficient signal exchange between cells of the innate and adaptive immune system and productive activation of the immune system . Furthermore, the type I IFN secreted by pDCs will activate more cells via binding to the type I IFN receptor, expressed on the surface of most cells, in a paracrine or autocrine manner . This in turn induces a feedback loop on the targeted cells, resulting on the one hand in the activation of these cells and the production, and secretion of more cytokines and chemokines, and on the other hand it will lead to the de‐activation of pDCs (and other cells) by initiating transcription factor pathways, that will inhibit type I IFN production, but also DC differentiation .…”

“…Furthermore, type I IFN secreted by activated DCs will activate surrounding cells via binding to the type I IFN receptor, expressed on the surface of most cells, in a paracrine or autocrine manner . This in turn induces a feedback loop on the targeted cells, resulting on one hand in the activation of these cells, resulting in differentiation and maturation of progenitor cells, and on the other hand it also will lead to the de‐activation of DCs (and other cells) by initiating transcription factor pathways, that inhibit type I IFN production, but also DC differentiation .…”