Blockade of PD-L1/PD-1 signaling promotes osteo-/odontogenic differentiation through Ras activation / 国际口腔科学杂志·英文版
International Journal of Oral Science
;
(4): 18-18, 2022.
Article
in English
| WPRIM
| ID: wpr-929146
ABSTRACT
The programmed cell death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) deliver inhibitory signals to regulate immunological tolerance during immune-mediated diseases. However, the role of PD-1 signaling and its blockade effect on human dental pulp stem cells (hDPSCs) differentiation into the osteo-/odontogenic lineage remain unknown. We show here that PD-L1 expression, but not PD-1, is downregulated during osteo-/odontogenic differentiation of hDPSCs. Importantly, PD-L1/PD-1 signaling has been shown to negatively regulate the osteo-/odontogenic differentiation of hDPSCs. Mechanistically, depletion of either PD-L1 or PD-1 expression increased ERK and AKT phosphorylation levels through the upregulation of Ras enzyme activity, which plays a pivotal role during hDPSCs osteo-/odontogenic differentiation. Treatment with nivolumab (a human anti-PD-1 monoclonal antibody), which targets PD-1 to prevent PD-L1 binding, successfully enhanced osteo-/odontogenic differentiation of hDPSCs through enhanced Ras activity-mediated phosphorylation of ERK and AKT. Our findings underscore that downregulation of PD-L1 expression accompanies during osteo-/odontogenic differentiation, and hDPSCs-intrinsic PD-1 signaling inhibits osteo-/odontogenic differentiation. These findings provide a significant basis that PD-1 blockade could be effective immunotherapeutic strategies in hDPSCs-mediated dental pulp regeneration.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Regeneration
/
Stem Cells
/
Dental Pulp
/
B7-H1 Antigen
/
Programmed Cell Death 1 Receptor
Limits:
Humans
Language:
English
Journal:
International Journal of Oral Science
Year:
2022
Type:
Article
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