. Author manuscript; available in PMC: 2024 Nov 1.

Published in final edited form as: Semin Immunol. 2023 Aug 29;70:101835. doi: 10.1016/j.smim.2023.101835

Table 2.

Transcriptional heterogeneity of lymphatic endothelial cells.

Type of LEC	LEC subpopulations	Localization	Unique transcriptomic signature	Function	References
Subcapsular sinus LEC	Ceiling LEC (cLEC)	Lining the ceiling of SCS space	Lyve1⁺, Cav1⁺, Ackr3⁺, Ackr4⁺, Cd36⁺	(1) cLEC express chemokine scavenging receptors (ACKR3 and 4) that might shape chemokine gradient by scavenging homeostatic chemokines, CCL19, CCL21, and CCL25, close to the capsular region. (2) cLEC also expresses lipid transporters (CD36) that may help uptake the low-density lipoproteins (LDLs) from incoming lymph from afferent lymphatics.	[93–95, 201]
Subcapsular sinus LEC	Floor LEC (fLEC)	Lining the floor of SCS space	Lyve1⁺, Cd44⁺, cd74⁺, Cd274^hi, Madcam1⁺, Ccl20⁺, Cxcl1⁺, Cxcl5⁺	(1) fLEC express Class II MHC molecules, invariant chain CD74, and high levels of PD-L1, suggesting their possible role in maintaining tolerance. (2) fLEC are capable of chemoattraction of CCR6⁺ Th17, γδT cells and ILC3s via CCL20. (3) fLEC may interact with incoming immune cells from afferent lymphatics via multiple cell adhesion molecules (MAdCAM1, Lyve1, GlyCAM1) and integrins.	[93–95]
Medullary sinus LEC	Ptx3⁺ LEC	Cortical and medullary sinus lymphatics	Lyve1⁺, Ptx3⁺, Cd274^lo, Marco⁻, Itih5⁺, Mrc1⁺, Reln⁺	Ptx3⁺ LEC identified in mice but not human LN. Ptx3 is known to bind to soluble pattern recognition and altered self-molecules that help promote innate recognition and phagocytic activity. (3) Ptx3 LEC also interact with CD44^hi activated/memory T cells via MRC-1. (4) Ptx3⁺ LEC may vigorously respond to the angiogenic signals due to their higher expression of VEGFR3.	[93–95]
Medullary sinus LEC	Marco⁺ LEC	Medullary sinus lymphatics	Lyve1⁺, Marco⁺, Cd209⁺, Clec1b⁺, Clec4g⁺, Clec4m⁺	Marco⁺ LEC expresses CLEC2 (Clec1b), a ligand for PDPN, and like CLEC2⁺ DCs, these cells may have a role in FRC stretching and expansion. (2) Marco LEC abundantly express a gene signature indicative of their possible role in maintaining innate immune response in the medullary region. (3) These cells are also shown to sequester virus particles to limit dissemination.	[93–95, 202]
	Valve LEC (vLEC)	Throughout the lymphatic network	Lyve1⁺, Foxc2⁺, Cav1⁺, Esam⁺,Cldn11⁺	Prevent the backflow of lymph and facilitate the unidirectional flow of lymph though lymphatics.	[93–95, 203]