Polysialylation controls dendritic cell trafficking by regulating chemokine recognition

Area of Science:

• Glycoscience
• Immunology
• Cellular Biology

Background:

• Polysialylation is a rare posttranslational modification of glycans, primarily known for its role in nervous system development and plasticity.
• Chemokine receptors, such as CCR7, are critical for regulating immune cell migration to lymphoid organs.

Purpose of the Study:

• To investigate the role of polysialylation in immune cell trafficking.
• To determine if polysialylation modifies the function of the chemokine receptor CCR7 and its interaction with its ligand CCL21.

Main Methods:

• Analysis of polysialylation on CCR7 in wild-type and polysialyltransferase-deficient mice.
• Assessment of dendritic cell trafficking and lymph node homeostasis.
• Structure-function analysis of chemokine-receptor interactions.

Main Results:

• CCR7, the key chemokine receptor for immune cell trafficking, is modified by polysialic acid.
• Polysialylation of CCR7 is essential for the recognition of its ligand, CCL21.
• Mice deficient in polysialyltransferase exhibit impaired dendritic cell trafficking, disrupted lymph node homeostasis, and unresponsiveness to inflammatory stimuli.
• Structural analysis shows polysialic acid releases CCL21 from an autoinhibited conformation.

Conclusions:

• Polysialylation is a critical regulator of immune cell trafficking by modulating chemokine receptor function.
• This study identifies a novel glycosylation-mediated immune cell trafficking disorder.
• The findings elucidate the mechanistic basis of how polysialic acid influences chemokine-receptor interactions and immune responses.