Journal
SCIENCE
Volume 325, Issue 5940, Pages 612-616Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1175202
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Funding
- NIH [U01 HL080731, P50 CA86355, R24 CA69246, U54 CA126515, P01 A154904, 1R01HL095612]
- MGH-Center for Systems Biology
- AHA [SDG 0835623D]
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A current paradigm states that monocytes circulate freely and patrol blood vessels but differentiate irreversibly into dendritic cells (DCs) or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation.
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