Journal
SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41598-021-84023-0
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Funding
- CNRS
- INSERM
- Fondation pour l'Aide a la Recherche sur la Sclerose en Plaques (ARSEP)
- The Secular Society (TSS)
- TSS
- Region Ile de France, Domaine d'Interet Majeur Ile de France Biotherapies
- Association pour la Recherche contre le Cancer (ARC)
- ARSEP
- Greek Scholarship IKY
- NIH [R01 HL126166, R01 HL139008]
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Early innate education in the bone marrow primes hematopoietic progenitors for trained immunity or immunoregulatory functions. Activation of pDC precursors within the bone marrow can halt progression of autoimmune diseases, offering promising perspectives for cell therapy.
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-beta, and after migration, of enhanced levels of IL-27. CpG-pre-pDC derived TGF-beta 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-beta 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.
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