Sphingosine-1-phosphate lyase is expressed by CD68+ cells on the parenchymal side of marginal reticular cells in human lymph nodes.
Lymph nodes (LNs) form the intersection between the vascular and lymphatic systems. Lymphocytes and antigen-presenting cells (APCs) traffic between these systems, but the barriers crossed during this trafficking in human LNs are poorly defined. We identified a population of cells in human LNs that lines the boundary between the parenchyma and lymphatic sinuses, consistent with descriptions of marginal reticular cells (MRCs) in murine LNs. Human MRCs are CD141(high) podoplanin(+), CD90(+), ICAM1(+), and VCAM1(+) but lack endothelial and hematopoietic cell markers, or alpha-smooth muscle actin. We then examined expression of the enzyme sphingosine-1-phosphate (S1P) lyase (SGPL1) relative to the boundary defined by MRCs. SGPL1 expression was almost exclusively restricted to cells on the parenchymal side of MRCs, consistent with a role in maintaining the S1P gradient between the sinuses and the parenchyma. Surprisingly the cells expressing SGPL1 in the parenchyma were CD68(+) APCs. CD68(+) APCs generated from human monocytes were able to internalize and irreversibly degrade S1P, and this activity was inhibited by the S1P analogue FTY720. This work provides a map of the key structures at the boundary where human lymphocytes egress into sinuses, and identifies a novel potential mechanism for the activity of S1P analogues in humans.
School of Biological Sciences, The University of Auckland, Auckland, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand.
Saem Mul
SM
Park
Catherine E
CE
Angel
Julie D
JD
McIntosh
Anna E S
AE
Brooks
Martin
M
Middleditch
Chun-Jen J
CJ
Chen
Katya
K
Ruggiero
Jonathan
J
Cebon
P
P
Rod Dunbar
D000446:Aldehyde-Lyases / Q000096:biosynthesis*; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D008208:Lymphatic System / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D058503:Mesophyll Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D000097382:CD68 Molecule
D000446:Aldehyde-Lyases; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D008246:Lysophospholipids; D013110:Sphingosine; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C060506:sphingosine 1-phosphate; C022649:sphingosine 1-phosphate lyase (aldolase)
FTY720; Lymph node; Lymphocyte egress; Marginal reticular cells; Sphingosine 1-phosphate