Marsman, Casper and Lafouresse, Fanny and Liao, Yang and Baldwin, Tracey M. and Mielke, Lisa A. and Hu, Yifang and Mack, Matthias and Hertzog, Paul J. and de Graaf, Carolyn A. and Shi, Wei and Groom, Joanna R. (2018) Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation. IMMUNOLOGY AND CELL BIOLOGY, 96 (10). pp. 1083-1094. ISSN 0818-9641, 1440-1711
Full text not available from this repository. (Request a copy)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 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYSTEMIC-LUPUS-ERYTHEMATOSUS; CUTTING EDGE; I INTERFERON; T-CELLS; RECEPTOR; RESPONSES; ALPHA; CXCR3; IMMUNITY; TISSUES; Chemokine; conventional DC; CXCR3; IFNAR1; IMQ; plasmacytoid DC; SLE; TLR7; type 1 IFN |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Oct 2019 09:05 |
| Last Modified: | 10 Oct 2019 09:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13595 |
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