Identity, ontogeny, and age-related changes in splenic white pulp macrophages in mouse and human spleen

Area of Science:

• Immunology
• Cell Biology
• Aging Research

Background:

• The spleen harbors diverse macrophage populations crucial for immune surveillance and homeostasis.
• The ontogeny, transcriptomic identity, and aging dynamics of splenic macrophages remain poorly understood.
• The existence of homologous macrophage populations in the human spleen is unknown.

Purpose of the Study:

• To elucidate the origins, self-renewal mechanisms, and aging-related changes of splenic macrophage subsets in mice.
• To identify homologous macrophage populations in the human spleen and compare their aging dynamics with mouse counterparts.

Main Methods:

• Single-cell RNA sequencing and lineage tracing in mice.
• Comparative analysis of mouse and human splenic macrophage populations.
• Assessment of macrophage abundance and distribution during aging.

Main Results:

• Mouse marginal zone macrophages (MZM) and marginal zone metallophilic macrophages (MMM) are tissue-resident, self-renewing populations, while tingible body macrophages (TBM) are monocyte-derived.
• MMM contribute to MZM maintenance, and monocytes can repopulate MMM after depletion.
• A decrease in MMM precedes other cellular changes during aging.
• Human TBM and perifollicular zone macrophages (PFZM) represent a single population homologous to mouse MZM and MMM.
• TBM abundance increases with age in both mice and humans.

Conclusions:

• Splenic macrophage populations exhibit distinct ontogenetic pathways and aging trajectories.
• Homologous macrophage populations exist in mouse and human spleens, with conserved age-related changes.
• Age-associated alterations in splenic macrophages may contribute to immunosenescence.