Neural crest-derived pericytes promote egress of mature thymocytes at the corticomedullary junction.
T cell egress from the thymus is essential for adaptive immunity, yet the requirements for and sites of egress are incompletely understood. We have shown that transgenic expression of sphingosine-1-phosphate receptor-1 (S1P1) in immature thymocytes leads to their perivascular accumulation and premature release into circulation. Using an intravascular procedure to label emigrating cells, we found that mature thymocytes exit via blood vessels at the corticomedullary junction. By deleting sphingosine kinases in neural crest-derived pericytes, we provide evidence that these specialized vessel-ensheathing cells contribute to the S1P that promotes thymic egress. Lymphatic endothelial cell-derived S1P was not required. These studies identify the major thymic egress route and suggest a role for pericytes in promoting reverse transmigration of cells across blood vessel endothelium.
Zachariah
Marcus A
MA
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, HSE1001, San Francisco, CA 94143, USA.
Cyster
Jason G
JG
D000818:Animals; D015551:Autoimmunity; D001808:Blood Vessels / Q000166:cytology / Q000502:physiology*; D002465:Cell Movement; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology; D042601:Lymphatic Vessels / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009432:Neural Crest / Q000166:cytology; D020286:Pericytes / Q000378:metabolism / Q000502:physiology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology; D013950:Thymus Gland / Q000098:blood supply* / Q000166:cytology*; D000099157:Sphingosine Kinase
D051741:Kruppel-Like Transcription Factors; D017853:Phosphotransferases (Alcohol Group Acceptor); D049349:Receptors, Lysosphingolipid; D000099157:Sphingosine Kinase; C498314:Klf2 protein, mouse