Human plasmacytoid dendritic cells interact with gp96 via CD91 and regulate inflammatory responses

Area of Science:

• Immunology
• Cell Biology

Background:

• Glucose-regulated stress protein gp96 is implicated in host defense against pathogens and cancer.
• Plasmacytoid dendritic cells (pDCs) are key immune cells involved in initiating and regulating immune responses.

Purpose of the Study:

• To investigate the interaction between gp96 and human blood pDCs.
• To elucidate the receptor-mediated mechanisms and functional consequences of gp96 binding to pDCs.

Main Methods:

• Receptor identification using competition studies.
• Confocal microscopy for visualizing gp96 endocytosis and intracellular trafficking.
• Antibody-based detection of CD91 expression on pDCs.
• Analysis of NF-kappaB pathway activation and cytokine production.
• Assessment of pDC phenotype and function after gp96 treatment.

Main Results:

• gp96 directly binds to pDCs through the CD91 receptor.
• CD91 triggering leads to gp96 endocytosis and ER trafficking.
• pDC maturation up-regulates CD91 expression and gp96 binding.
• gp96-pDC interaction activates NF-kappaB, suppresses IL-8 release, and maintains an immature pDC phenotype.
• gp96-treated pDCs inhibit the activation of monocyte-derived dendritic cells.

Conclusions:

• gp96-pDC interaction via CD91 represents a regulatory mechanism controlling immune responses to extracellular gp96.
• This pathway may play a significant role in managing inflammation and wound healing processes.