Table 1. Innate immune cells and markers unique to the spleen.
Selected innate immune cells adapted to the murine spleen are shown with key markers, developmental pathways and location in the spleen at steady state. Markers in italics are expressed in subsets of the population. CSF1R (Colony stimulating factor 1 receptor)/CD115/MCSFR (Macrophage colony-stimulating factor receptor); CCR2 (Chemokine, cc motif receptor 2)/MCP-1R (Monocyte chemoattractant protein 1 receptor); XCR1 (X-C motif chemokine receptor 1); CLEC9A (C-type lectin domain containing 9A)/DNGR1 (DC NK lectin group receptor 1); DEC205/CD205; SIRPα (Signal regulatory protein alpha)/CD172α; DCIR2 (DC immunoreceptor 2)/33D1 staining/CLEC4A4 (C-type lectin domain family 4, member 4a); CX3CR1(C-X3-C motif chemokine receptor 1); (CD317/BST2 (BM stromal cell antigen 2)/PDCA1 (plasmacytoid DC Ag-1); SIGLECH (Sialic acid binding Ig-like lectin H); B220/PTPRC (Protein tyrosine phosphatase receptor type c)/LY5.
| Markers | Origin | Splenic Location |
Key transcription factors |
Function | |
|---|---|---|---|---|---|
| RP macrophage (16, 26) | CD11b+ F4/80+ CD68+ CD206+ Dectin-2+ VCAM+ | BM monocyte and fetal monocytes from yolk sac | RP | SPIC | Clearance of aged or foreign RBCs, iron recycling, heme breakdown |
| MZ macrophage (MZM) (16, 26) | CD209b/SIGN-R1+ MARCO+ SR-A+ ER-TR9+ CD68+ Dectin-2+ Tim4+ | Bone marrow monocyte | MZ | LXRα | Recognition of pathogens, activation of MZB cells |
| MZ metallophilic macrophage (MMM) (16, 26) | CD169/Siglec-1+/MOMA1 staining CD68+ | Bone marrow monocyte | At the interface of the WP and MZ | LXRα | Recognition of pathogens, speculated transfer of antigen from blood to WP |
| Tingible body macrophages (16) | MERTK+ TIM4+ F4/80−CD11b− CD68+MFG-E8+ | ? | GC DZ in B cell follicle | ? | Removal of apoptotic B cells |
| MZB cells (mouse) (20) (21) | IgM+ IgDlo CD21+CD23- CD1d+ B220lo | Transitional B cells | MZ | Aiolos | Rapid production of IgM antibodies and antigen trafficking to follicle |
| Inflammatory monocytes/TIP-DC (59) | CCR2+ CD115/CSF1R+ Ly6C+ Ly6G- F4/80+ CD11b+ MAC3+ CD11c+ | Bone marrow | Recruited to spleen from bone marrow via CCR2 | Mafb | TNF and NO production, bacterial clearance |
| cDC1(28, 30) | XCR1+ CD11c+ CD8αα+ CLEC9A/DNGR1+ DEC205+ CD207+ CD24+ CD103+ | Bone marrow CDP (common DC precursor) | RP/MZ and PALS of WP | BATF3, IRF8 | Cross-presentation, CD8+ T cell activation |
| cDC2(28, 30) | CD11c+ CD11b+ DCIR2/33D1 staining SIRPα/CD172+ ESAM+ CD4+ CX3CR1+ | Bone marrow CDP | Bridging channel | Notch2, IRF4, KLF4 | MHC II antigen processing, CD4+ T cell activation |