Scrib and Dlg1 polarity proteins regulate Ag presentation in human dendritic cells

Area of Science:

• Immunology
• Cell Biology
• Virology

Background:

• PDZ polarity proteins Scrib and Dlg1 are expressed and regulated in human antigen-presenting cells (APCs), including dendritic cells (DCs).
• Influenza A virus NS1 protein targets Scrib and Dlg1 in human DCs.
• Known functions of Scrib and Dlg1 in other immune cells (macrophages, T cells) suggest potential roles in DCs, but these remain uncharacterized.

Purpose of the Study:

• To investigate the functions of Scrib and Dlg1 in human dendritic cells (DCs).
• To determine the impact of Scrib and Dlg1 depletion on DC maturation, co-stimulatory molecule expression, and cytokine production.
• To assess the effect of Scrib and Dlg1 deficiency in DCs on T cell activation.

Main Methods:

• Knockdown of Scrib and Dlg1 expression in human DCs.
• Evaluation of co-stimulatory molecule expression (e.g., CD86, CD83) during DC maturation.
• Measurement of cytokine production (e.g., IL-6, IL-12) by mature DCs.
• Assessment of T cell activation following co-culture with Scrib or Dlg1-depleted DCs.

Main Results:

• Scrib knockdown impaired CD86 expression, while Dlg1 knockdown affected CD83 up-regulation and IL-6 production.
• Both Scrib and Dlg1 were essential for adequate IL-12 production after DC maturation.
• Depletion of Scrib or Dlg1 resulted in inefficient DC maturation.
• Impaired DC maturation due to Scrib or Dlg1 depletion led to reduced T cell activation.

Conclusions:

• Scrib and Dlg1 play distinct roles in human DC maturation pathways.
• Both Scrib and Dlg1 are critical for optimal IL-12 production in mature DCs.
• Scrib and Dlg1 are essential for effective T cell activation mediated by human DCs, impacting both innate and adaptive immunity.