Objective:

To critically examine the role of plasmacytoid dendritic cells (pDCs) in the immunopathogenesis of systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE), highlighting their significance in disease progression and treatment.

Key Findings:

• pDCs play a central role in the pathogenesis of SLE and CLE through dysregulated production of type I interferon (IFN-I), which is crucial for understanding treatment responses.
• SLE is characterized by multisystem involvement and autoantibody production, while CLE primarily affects the skin, necessitating different therapeutic approaches.
• Current treatments for SLE include biologics targeting immune pathways, but there are no approved treatments specifically for CLE, highlighting a significant treatment gap.

Interpretation:

Understanding the role of pDCs in IFN-I production is crucial for developing targeted therapies that improve patient outcomes in SLE and CLE, potentially leading to more effective management strategies.

Limitations:

• Limited understanding of the pathophysiological loss of IFN pathway negative feedback, which complicates treatment development.
• Complexity of IFN production by non-pDC cells and the role of different cytokines and chemokines, which may hinder targeted therapy.
• Variability in pDC activation and effects in SLE versus CLE, impacting the predictability of treatment responses.

Conclusion:

Expanding knowledge on pDCs and their role in lupus pathogenesis is urgent and may lead to more effective and targeted treatment strategies, ultimately improving patient outcomes.