CCL5-producing migratory dendritic cells guide CCR5+ monocytes into the draining lymph nodes

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Dendritic cells (DCs) and monocytes are crucial for antigen presentation in lymph nodes (LNs) via a CCR7-dependent pathway.
• The mechanism by which monocytes, unlike migratory DCs, reach LNs remains unclear, as they typically do not express CCR7.

Purpose of the Study:

• To elucidate the migration pathways of monocytes and conventional DCs (cDCs) to LNs.
• To understand the role of chemokine receptors and ligands in the homing of these immune cells.
• To investigate how antigen exposure influences the migration and interaction of DCs and monocytes in LNs.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) to analyze gene expression profiles of LN mononuclear phagocytes.
• Two distinct tracking methods to monitor antigen-capturing cell populations in the lung and their migration to LNs.
• Analysis of antigen presentation in genetically modified mice deficient in specific chemokine receptors (Ccl5, Ccr2, Ccr5, Ccr7, Batf3).

Main Results:

• scRNA-seq identified monocytes and various DC subsets in LNs, with migratory cDCs upregulating Ccr7 and chemokines like Ccl5.
• Migratory monocytes expressed Ccr5, a receptor for Ccl5, suggesting a role in monocyte homing.
• Both CD88hiCD26lomonocytes and CD88-CD26hi cDCs captured inhaled antigens and migrated to LNs.
• Antigen-bearing DCs utilized CCR7 for LN entry, while monocytes were guided by CCR5 to follow CCL5-producing cDCs.

Conclusions:

• Monocytes utilize the CCR5-CCL5 axis to enter LNs by following migratory cDCs.
• This coordinated migration of DCs and monocytes is essential for regulating DC-mediated immunity.
• The study reveals distinct yet interconnected migratory mechanisms for DCs and monocytes in immune surveillance.