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Published on: November 4, 2016
Resiquimod-Mediated Activation of Plasmacytoid Dendritic Cells Is Amplified in Multiple Sclerosis
Marta Corsetti1, Gabriella Ruocco2, Serena Ruggieri3
1Neuroimmunology Unit, IRCSS Fondazione Santa Lucia, 00143 Rome, Italy. m.corsetti@hsantalucia.it.
Background:
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. The cause of multiple sclerosis is unknown but there are several evidences that associate the genetic basis of the disease with environmental causes. An important association between viral infection and development of MS is clearly demonstrated. Viruses have a strong impact on innate immune cells. In particular, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), are able to respond to viruses and to activate the adaptive immune response.
Methods:
In this study we mimic viral infection using synthetic single-strand RNA, Resiquimod, and we compared the response of both DC subsets derived from healthy donors and MS patients by characterizing the expression of costimulatory molecules on the DC surface.
Results:
We found that pDCs from MS patients express higher levels of OX40-L, HLA-DR, and CD86 than healthy donors. Moreover, we found that blood cells from MS patients and healthy donors upon Resiquimod-stimulation are enriched in a subpopulation of pDCs, characterized by a high amount of costimulatory molecules.
Conclusion:
Overall, these results indicate that activation of pDCs is enhanced in MS, likely due to a latent viral infection, and that costimulatory molecules expressed on pDCs could mediate a protective response against the viral trigger of autoimmunity.
Insights
Plasmacytoid dendritic cells (pDCs) show enhanced activation in multiple sclerosis (MS) patients, potentially due to viral infections. These pDCs express higher costimulatory molecules, suggesting a protective role against viral triggers in MS.
Area of Science:
- Immunology
- Neuroscience
- Virology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system.
- Genetic and environmental factors, including viral infections, are implicated in MS pathogenesis.
- Dendritic cells (DCs), including myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), play a crucial role in antiviral responses and adaptive immunity.
Purpose of the Study:
- To investigate the response of pDCs and mDCs to viral mimicry in multiple sclerosis patients.
- To compare the expression of costimulatory molecules on DCs from healthy donors and MS patients upon stimulation with a viral mimic.
Main Methods:
- Mimicked viral infection using synthetic single-strand RNA (Resiquimod).
- Compared the response of pDCs and mDCs from healthy donors and MS patients.
- Characterized the surface expression of costimulatory molecules on DCs.
Main Results:
- pDCs from MS patients exhibited higher expression of OX40-L, HLA-DR, and CD86 compared to healthy donors.
- Resiquimod stimulation enriched a subpopulation of pDCs with high costimulatory molecule expression in both MS patients and healthy donors.
- These findings suggest an enhanced activation state of pDCs in MS.
Conclusions:
- pDC activation appears to be heightened in multiple sclerosis, potentially linked to latent viral infections.
- The increased expression of costimulatory molecules on pDCs may represent a protective mechanism against viral triggers contributing to MS autoimmunity.
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