Submitted February 9, 2009
Accepted March 25, 2009
Lymphoid tissue specific homing of bone marrow-derived dendritic cells
Remi J. Creusot, Shahriar S. Yaghoubi, Pearl Chang, Justine Chia, Christopher H. Contag, Sanjiv S. Gambhir, and C. Garrison Fathman*
Department of Medicine, Division of Immunology & Rheumatology, Stanford University, Stanford, CA, United States
Department of Radiology, Molecular Imaging Program, Stanford University, Stanford, CA, United States
Department of Pediatrics, Stanford University, Stanford, CA, United States
* Corresponding author; email: cfathman{at}stanford.edu.
Because of their potent immunoregulatory capacity, dendritic cells (DCs) have been exploited as therapeutic tools to boost immune responses against tumors or pathogens, or dampen autoimmune or allergic responses. Murine bone marrow-derived DCs (BM-DCs) are the closest known equivalent of the blood monocyte-derived DCs that have been used for human therapy. Current imaging methods have proven unable to properly address the migration of injected DCs to small and deep tissues in mice and humans. This study presents the first extensive analysis of BM-DC homing to lymph nodes (and other selected tissues) after intravenous and intraperitoneal inoculation. Following intravenous delivery, DCs accumulated in the spleen, and preferentially in the pancreatic and lung-draining lymph nodes. In contrast, DCs injected intraperitoneally were found predominantly in peritoneal lymph nodes (pancreatic in particular), and in omentum-associated lymphoid tissue. This uneven distribution of BM-DCs, independent of the mouse strain and also observed within pancreatic lymph nodes, resulted in the uneven induction of an immune response in different lymphoid tissues. These data have important implications for the design of systemic cellular therapy with DCs, and in particular underlie a previously unsuspected potential for specific treatment of diseases such as autoimmune diabetes and pancreatic cancer.
