ILC2-derived LIF licences progress from tissue to systemic immunity

Area of Science:

• Immunology
• Cell Biology
• Respiratory Medicine

Background:

• Immune cell trafficking is crucial for surveillance and immune responses.
• Adhesion and chemokine receptors guide immune cells to specific tissues and lymphatic system.
• Group 2 innate lymphoid cells (ILC2s) play roles in tissue immunity.

Purpose of the Study:

• To investigate the role of leukaemia inhibitory factor (LIF) produced by ILC2s in immune cell migration from the lungs.
• To understand how LIF influences immune responses during viral infection and allergic challenge.
• To elucidate the mechanism by which ILC2s regulate immune cell homing to lymph nodes.

Main Methods:

• Investigated the impact of disrupted LIF production from ILC2s on immune cell migration.
• Analyzed immune cell distribution in lungs and lymph nodes following viral infection and allergen challenge.
• Examined the expression of chemokines (CCL21) and receptors (CCR7) in lymphatic endothelial cells and immune cells.

Main Results:

• Disruption of LIF production by ILC2s prevents immune cells from migrating from the lungs to lymph nodes.
• In the absence of LIF, plasmacytoid dendritic cells (pDCs) are retained in the lungs, enhancing local antiviral immunity.
• Chronic allergen challenge with absent LIF leads to immune cell accumulation and tertiary lymphoid structure formation in the lungs.
• ILC2-derived LIF induces CCL21 production in lymphatic endothelial cells, facilitating CCR7+ immune cell homing to lymph nodes.
• Failure of immune cell migration to lymphatics results in compromised lymph node reactions.

Conclusions:

• ILC2-derived LIF is a key regulator of immune cell egress from the lungs.
• LIF controls the balance between tissue-localized immunity and systemic immune responses.
• LIF production by ILC2s influences the immune system's response to both viral infections and allergens in the lungs.