ILC2s navigate tissue redistribution during infection using stage-specific S1P receptors

Area of Science:

• Immunology
• Cell Biology
• Lymphocyte Trafficking

Background:

• Circulating lymphocytes' recruitment to infection sites is well-understood.
• Mechanisms of tissue-resident lymphocyte recirculation remain less clear.
• Group 2 innate lymphoid cells (ILC2s) reside in tissues and can redistribute.

Purpose of the Study:

• To elucidate the molecular basis for intestinal ILC2 recirculation.
• To identify key molecules involved in ILC2 migration during helminth infection or IL-25 stimulation.

Main Methods:

• Investigated ILC2 redistribution in response to helminth infection or IL-25.
• Analyzed the role of the lymphatic vessel network in ILC2 migration.
• Examined epigenetic changes and sphingosine-1-phosphate receptor (S1PR) expression in ILC2s.
• Assessed the function of S1PR1 and S1PR5 in ILC2 egress from tissues and lymph nodes.
• Studied the impact of CD69 on S1PR1 function.

Main Results:

• ILC2 redistribution requires access to the lymphatic vessel network.
• IL-25 stimulation induces epigenetic changes and S1PR expression in intestinal ILC2s.
• S1PR5 is critical for ILC2 exit from intestinal tissue into lymph.
• S1PR1 mediates ILC2 egress from lymph nodes into blood circulation.
• CD69 expression influences S1PR1-dependent migration by causing S1PR1 internalization.

Conclusions:

• A stage-specific requirement for different S1P receptors governs ILC2 redistribution.
• ILC2 migration involves distinct S1PRs for exiting tissue versus entering circulation.
• Innate and adaptive lymphocytes share vascular networks but use specialized migration cues.