Table 1.
Summarizing table of the main molecular players described in Leukocyte traffic through LVs.
| LEC receptor/ligand | Leukocyte receptor/ligand | Experimental model | Key observations | Reference |
|---|---|---|---|---|
| CCL21 | CCR7 | DC and T adoptive transfer of CCR7−/−, LN analysis on CCR7−/−mice, IVM of footpad | DC, lymphocytes, and neutrophils fail to migrate into LVs to LNs both under steady-state and inflammatory conditions | (11, 34, 40, 41, 67, 78) |
| CXCL12 | CXCR4 | FITC painting in the presence of a chemical inhibitor, transwell assays, inflammation models | Impaired DC migration to LN when treated with inhibitor. Induces transmigration across LEC in transwell assays. Impaired CHS response when inhibited | (62, 85) |
| S1P | S1PR1-5 | FITC painting in the presence of chemical inhibitor FTY720, DC analysis in LN under inflammation and in the presence of inhibitor, adoptive skin transfer of T lymphocytes, and whole mount immunofluorescence after ear injection in FTY720 treated cells | Impaired DC and T cell migration from skin to LNs. Induced by inhibitor. Impaired in vitro trans-endothelial migration in LVs. Induces transmigration across LEC in transwell assays | (54, 91, 92, 97) |
| D6 | Inflammatory chemokines | Immunofluorescence of skin LVs and LNs and study of LN DC populations after TPA induced inflammation in D6−/−mice | Accumulated inflammatory cells blocking LV function and other DC migration in D6−/−mice | (105) |
| CX3CL1 | CX3CR1 | FITC painting in CHS preinflamed skin in the presence of CX3CL1 Abs, adoptive transfer of CX3CL1−/−BMDCs, transwell assays | DC migration to LN is delayed. Impaired in vitro migration when the chemokine or its secretion is blocked. Effects only observed under inflammation | (99) |
| PECAM | PECAM | Transwell assays, ex vivo human skin culture in the presence of blocking Ab, immunofluorescence, and DC count inside LVs | Impaired trans-endothelial migration and intravasation in human skin explants, evidence provided only in human | (62) |
| ICAM-1 | CD11a,b | FITC painting in the presence of blocking antibodies or in ICAM-1 deficient mouse, BMDC adoptive transfer in the presence of blocking Abs or from CD18−/−mice, whole mount immunofluorescence of ears after DC injection, transwell assays | In inflammatory and high flow conditions Blockade of ICAM-1 and blockade or β2 integrins inhibit trans-endothelial migration and DC migration to LN | (29, 33, 56, 107, 108) |
| VCAM | VLA-4 | BMDC adoptive transfer in the presence of blocking Abs, transwell assays | LN impaired DC migration under inflammation and impaired in vitro trans-endothelial migration | (29) |
| CD99 | PILR | Transwell assays, ex vivo human skin culture in the presence of blocking Ab, immunofluorescence, and DC count inside LVs | Impaired trans-endothelial migration and intravasation in human skin explants, evidence provided only in human | (62) |
| L1CAM | L1CAM | FITC painting assays in mice deficient in L1CAM under Tie 2 promoter, transwell, and adhesion assays | Impaired adhesion, transmigration in human (moDC) and mice (BMDC), impaired migration to LN | (52) |
| ALCAM | CD6 | Lung injection of FITC microbeads in ALCAM−/−mice | Impaired DC arrival to LNs in ALCAM−/−mice | (119) |
| Podoplanin | CLEC-2 | FITC painting in CLEC1b−/−mice, adoptive transfer of CLEC1b−/−DC, immunofluorescence of mice ear dermis cultured with BMDC | Impaired arrival of DC to LN, impaired intravasation, importance for protrusion formation | (123) |
| JAM-A | JAM-A | CHS response and FITC painting in Jam-A−/−and adoptive transfer of Jam-A deficient BM DCs, transwell assays | Jam-A ablation increases DC migration to LN and CHS responses as well as in vitro TEM | (161) |
| CLEVER-1 | – | Adoptive lymphocyte transfer in the presence of blocking Abs in mice and rabbit | Lymph node migration of lymphocytes is blocked | (127) |
| Mannose receptor | Glycoproteins | Adoptive lymphocyte transfer in footpad of MR−/−mice and IF of LNs | Lymphocyte migration to LN and adhesion to LEC in LNs is impaired | (130) |
| Semaphorin 3A | Plexin-A1 | Adoptive transfer of Plexin-A1−/−BMDCs, or wt DCs in Sema3A−/−mice, functional studies of T cell responses upon OVA skin sensitization in Plexin-A1−/−mice. In vitro videomicroscopy | Both, Plexin-A1 and Sema3A absence impairs DC migration to LNs. Sema3A is able to induce actomyosin contraction in BMDCs | (125) |
The table includes ligands expressed on both leukocyte and LEC, the evidence provided in leukocyte traffic and the experimental approach performed.