Lymphoid-tissue-specific homing of bone-marrow-derived dendritic cells.

Abstract:

: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. After 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 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.

journal_name

Blood

journal_title

Blood

authors

Creusot RJ,Yaghoubi SS,Chang P,Chia J,Contag CH,Gambhir SS,Fathman CG

doi

10.1182/blood-2009-02-204321

subject

Has Abstract

pub_date

2009-06-25 00:00:00

pages

6638-47

issue

26

eissn

0006-4971

issn

1528-0020

pii

blood-2009-02-204321

journal_volume

113

pub_type

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