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

ABSTRACT: 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 down-stream 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. In all DC subsets, type I IFNs were the main inducer of CXCR3 chemokines, as IFNAR receptor blocking or deficiency completely abrogated reporter expression. Chemoki ne 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE113770 | GEO | 2018/06/24

REPOSITORIES: GEO

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

Project description:We have used chemokine reporter mice to investigate down-stream effectors of type I IFN signaling, the chemokines of the CXCR3 family. We show that pDCs and conventional DCs display unique chemokine expression profiles that are dependent on IFNAR1 signaling. We go onto show that, following stimulation, pDCs form two stable and transcriptionally distinct populations based on their expression of CXCL10.

2019-12-26 | GSE110975 | GEO

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Microarray analysis of minor salivary glands from patients with primary Sjögren’s syndrome (SS) or non-SS

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Cxcl10 and Cxcr3 regulate self-renewal and differentiation of hematopoietic stem cells

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RNAseq of CD8 T-cells stimulated with CXCR3 chemokines

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