Table 2.
Potential targets of leukocyte–lymphatic interaction.
| Immune Cell | Immune Cell Interactor | Lymphatic Vessel Interactor | Purpose/Notes | Demonstrated interaction in | |
|---|---|---|---|---|---|
| Peripheral lymphatics | CNS-associated lymphatics | ||||
| Dendritic Cells | CCR7 | CCL21/19 | Chemoattractant: migration/recruitment |
193
194
195 |
14
36 |
| CXCR4 | CXCL12 | Chemoattractant: migration/recruitment |
105
196 |
— | |
| CX3CR1 | CX3CL1 | DC transmigration | 197 | — | |
| CLEC2 | PDPN | LEC adhesion, motility | 198 | — | |
|
Hyaluronan (hyaluronic
acid, HA |
Lyve-1 | LEC adhesion, DC transmigration | 199 | — | |
| Integrin β1 | VCAM-1 | LEC adhesion, DC transmigration |
200
201 |
37 | |
| Mac-1 | ICAM-1 | LEC adhesion, DC transmigration |
200
202 |
— | |
| CD137L | CD137 | Promotes CCL21-driven DC migration | 203 | — | |
| VEGF-C | VEGFR-3 | Lymphangiogenesis | 204 | 36 | |
| ()? | Clever-1 | Transmigration, tolerance | 205 | — | |
| Plexin A1 - NRP1 complex | SEMA3A | LEC adhesion, DC transmigration | 206 | — | |
| CD31† | CD31 | LEC adhesion, DC transmigration | 196 | — | |
| CD99† | CD99 | LEC adhesion, DC transmigration | 196 | — | |
| CD171/L1CAM† | CD171/L1CAM | LEC adhesion, DC transmigration | 207 | — | |
|
Macrophages
/Monocytes |
VEGF-C, -D, and -A | VEGFR-2, -3 | Lymphangiogenesis | 208 | 36 |
| CCR2 | CCL2 | Lymphangiogenesis - Recruitment of VEGF expressing Macrophages/Monocytes | 209 |
36
37 |
|
| T Cells | CCR7 | CCL21/19 | Chemoattractant migration/recruitment | 210 |
10
14 |
| CCR10 | CCL27 | Chemoattractant migration/recruitment | 211 | — | |
| LFA-1 | ICAM-1 | LEC adhesion, T cell transmigration | 212 | — | |
| PD-1 | PD-L1 | Immune Checkpoint/Tolerance |
154, 213 |
37 | |
| TCR | MHC-I | Priming, tolerance | 214 | — | |
| TCR | MHC-II | Priming. tolerance | 215 | 37 | |
| IDO induced reprogramming | IDO | Tolerance | 216 | — | |
| iNOS induced reprogramming | iNOS | Immunosuppressive | 217 | — | |
| ()? | Clever-1 | LEC adhesion, T cell transmigration | 218 | — | |
| IFN-γ (Th1) | IFN-γ Receptor | Suppression of lymphatic vessel growth A,B
Upregulation of PD-L1 C, IDO D, iNOS E |
219
A
220 B 216 D 217 E |
37 C | |
| B Cells | VEGF-A | VEGFR-2 | Lymphangiogenesis |
221
175 |
— |
| Neutrophils | CXCR4 | CXCL12 | Chemoattractant migration/recruitment | 188 | — |
| CCR7 | CCL21/19 | Chemoattractant migration/recruitment | 186 | — | |
| VEGF-D | VEGFR-2/3 | Lymphangiogenesis | 222 | — | |
List of some investigated targets of immune cell – lymphatic interactions, their function, and references organized according to anatomical region of investigation (Peripheral vs CNS lymphatics). Note this is not an exhaustive list, only potential targets as direct investigations into CNS lymphatic-leukocyte interactions are limited. Symbols: "—", interaction has no reference demonstrating evidence at this region. "?", binding site is not fully understood; proposed homophilic leukocyte – lymphatic interactions may also have heterophilic binding interactions, additional work is needed to fully map all binding interactions on leukocytes. Uppercase letters signify specific reference which applies to purpose of interaction.