T Cell Zone Resident Macrophages Silently Dispose of Apoptotic Cells in the Lymph Node

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SUMMARYIn lymph nodes (LNs), dendritic cells (DCs) are thought to dispose of apoptotic cells, a function pertaining to macrophages in other tissues. We found that a population of CX3CR1+ MERTK+ cells located in the T cell zone of LNs, previously identified as DCs, are efferocytic macrophages. Lineage-tracing experiments and shield chimeras indicated that these T zone macrophages (TZM) are long-lived macrophages seeded in utero and slowly replaced by blood monocytes after birth. Imaging the LNs of mice in which TZM and DCs express different fluorescent proteins revealed that TZM—and not DCs—act as the only professional scavengers, clearing apoptotic cells in the LN T cell zone in a CX3CR1-dependent manner. Furthermore, similar to other macrophages, TZM appear inefficient in priming CD4 T cells. Thus, efferocytosis and T cell activation in the LN are uncoupled processes designated to macrophages and DCs, respectively, with implications to the maintenance of immune homeostasis.Graphical AbstractHighlightsCX3CR1hi CD64+ MERTK+ macrophages form a dense network in the LN T cell zoneThese T cell zone macrophages (TZM), not CD8α DC, are the major local efferocytic cellsTZM are seeded in utero and are slowly replaced by BM derived monocytesDespite expressing activation molecules, TZM do not prime or tolerize CD4 naive T cellsDendritic cells (DCs) in the lymph node (LN) T cell zone are thought to be central to the clearance of apoptotic cells and T cell priming. Baratin et al. identify a population of LN macrophages that act as the sole professional scavengers in this area, suggesting that silent efferocytosis and T cell activation in the LN paracortex involve two different cell types—macrophages and DCs, respectively.

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