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Sphingosine 1-phosphate receptor agonism impairs skin dendritic cell migration and homing to secondary lymphoid tissue: Association with prolonged allograft survival
- Source :
- Transplant Immunology. 20:88-94
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- The novel immunomodulator FTY720 is a prototypic sphingosine-1-phosphate (S1P) receptor agonist that regulates lymphocyte migration and prolongs allograft survival. Skin dendritic cells (DC) play important roles in cutaneous immunity. We investigated the migration and function of skin DC exposed to FTY720 in vivo, or to its metabolite FTY720 phosphate (P) in vitro. C57BL/10 (H2(b)) recipient (but not donor) FTY720 treatment prolonged median skin C3H (H2(k)) allograft survival significantly, from 12 to 34.5 days. Non-transplanted, FTY720-treated mice revealed a marked increase in skin DC, although total DC in skin-draining lymph nodes (DLN) were unchanged compared with controls. Fewer allogeneic donor DC migrated to DLN of FTY720-treated graft recipients. DC that migrated from the skin of FTY720-treated mice showed reduced MHC class II, CD86 and CCR7 expression, suggesting impaired migratory potential to secondary lymphoid tissue, that correlated with DC retention in skin, and reduced T cell stimulatory activity. Fewer DC migrated from normal skin explants exposed to the FTY720 metabolite, FTY720P than to control medium. DC that did migrate expressed lower levels of MHC class II, CD86 and CCR7, and inferior T cell stimulatory ability. These data demonstrate S1P signaling regulates skin DC trafficking and modulates MHC class II, costimulatory, and homing receptor molecule expression that impairs their ability to elicit allogeneic T cell responses.
- Subjects :
- Graft Rejection
Male
Receptors, CCR7
T cell
Lymphocyte
Immunology
C-C chemokine receptor type 7
Biology
Mice
Cell Movement
Sphingosine
hemic and lymphatic diseases
medicine
Animals
Transplantation, Homologous
Immunology and Allergy
Dendritic cell migration
Receptor
CD86
Mice, Inbred C3H
Transplantation
MHC class II
integumentary system
Fingolimod Hydrochloride
Graft Survival
Histocompatibility Antigens Class II
Skin Transplantation
Organophosphates
Mice, Inbred C57BL
Receptors, Lysosphingolipid
medicine.anatomical_structure
Propylene Glycols
Langerhans Cells
Cancer research
biology.protein
B7-2 Antigen
Lymph Nodes
Immunosuppressive Agents
Subjects
Details
- ISSN :
- 09663274
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Transplant Immunology
- Accession number :
- edsair.doi.dedup.....a6f8c496a470dffd769cef66a145c075