Cell shape sensing licenses dendritic cells for homeostatic migration to lymph nodes

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• Immune cells undergo significant shape changes during tissue migration due to physical constraints.
• Dedicated shape-sensing pathways allow cells to adapt to deformation, but their impact on immune cell function is largely unknown.

Purpose of the Study:

• To identify a shape-sensing mechanism that regulates immune cell migration and function.
• To elucidate the molecular players and pathways involved in cell shape sensing during immune cell migration.

Main Methods:

• Investigated dendritic cell migration from peripheral tissues to lymph nodes.
• Utilized studies on the lipid metabolism enzyme cPLA2, nuclear envelope tensioning, and the ARP2/3 actin nucleation complex.
• Analyzed the activation of the IKKβ-NF-κB pathway and its effect on dendritic cell transcription.

Main Results:

• Identified a shape-sensing mechanism that enhances chemokine receptor CCR7 expression, directing dendritic cell migration.
• Demonstrated that this mechanism depends on cPLA2, nuclear envelope tension, and the ARP2/3 complex.
• Showed that cell shape sensing reprograms dendritic cell transcription via the IKKβ-NF-κB pathway, influencing tolerogenic potential.

Conclusions:

• Cell shape changes are critical for defining immune cell migratory behavior and immunoregulatory properties.
• Tissue physical properties significantly contribute to adaptive immunity through immune cell shape sensing.
• This study reveals a novel link between cellular mechanics and immune system regulation.