Toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis

Sci Rep. 2021 Feb 26;11(1):4735. doi: 10.1038/s41598-021-84023-0.


Early innate education of hematopoietic progenitors within the bone marrow (BM) stably primes them for either trained immunity or instead immunoregulatory functions. We herein demonstrate that in vivo or in vitro activation within the BM via Toll-like receptor-9 generates a population of plasmacytoid dendritic cell (pDC) precursors (CpG-pre-pDCs) that, unlike pDC precursors isolated from PBS-incubated BM (PBS-pre-pDCs), are endowed with the capacity to halt progression of ongoing experimental autoimmune encephalomyelitis. CpG activation enhances the selective migration of pDC precursors to the inflamed spinal cord, induces their immediate production of TGF-β, and after migration, of enhanced levels of IL-27. CpG-pre-pDC derived TGF-β and IL-27 ensure protection at early and late phases of the disease, respectively. Spinal cords of CpG-pre-pDC-protected recipient mice display enhanced percentages of host-derived pDCs expressing TGF-β as well as an accumulation of IL-10 producing B cells and of CD11c+ CD11b+ dendritic cells. These results reveal that pDC precursors are conferred stable therapeutic properties by early innate activation within the BM. They further extend to the pDC lineage promising perspectives for cell therapy of autoimmune diseases with innate activated hematopoietic precursor cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Interleukin-27 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology*
  • Spinal Cord / cytology*
  • Spinal Cord / immunology
  • Spinal Cord / metabolism
  • Toll-Like Receptor 9
  • Transforming Growth Factor beta / metabolism


  • Interleukin-27
  • Toll-Like Receptor 9
  • Transforming Growth Factor beta