Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation. Academic Article uri icon

Overview

abstract

  • Chemokines control the migratory patterns and positioning of immune cells to organize immune responses to pathogens. However, many chemokines have been associated with systemic autoimmune diseases that have chronic IFN signatures. We report that a series of chemokines, including CXCL4, CXCL10, CXCL12, and CCL5, can superinduce type I IFN (IFN-I) by TLR9-activated plasmacytoid DCs (pDCs), independently of their respective known chemokine receptors. Mechanistically, we show that chemokines such as CXCL4 mediate transcriptional and epigenetic changes in pDCs, mostly targeted to the IFN-I pathways. We describe that chemokines physically interact with DNA to form nanoparticles that promote clathrin-mediated cellular uptake and delivery of DNA in the early endosomes of pDCs. Using two separate mouse models of skin inflammation, we observed the presence of CXCL4 associated with DNA in vivo. These data reveal a noncanonical role for chemokines to serve as nucleic acid delivery vectors to modulate TLR signaling, with implications for the chronic presence of IFN-I by pDCs in autoimmune diseases.

publication date

  • May 31, 2022

Research

keywords

  • Chemokines
  • Dendritic Cells
  • Nanoparticles
  • Toll-Like Receptors

Identity

PubMed Central ID

  • PMC9161158

Scopus Document Identifier

  • 85131194774

Digital Object Identifier (DOI)

  • 10.1186/gb-2008-9-9-r137

PubMed ID

  • 35640018

Additional Document Info

volume

  • 219

issue

  • 7