NDLI: FLT3-ligand treatment of humanized mice results in the generation of large numbers of CD141+ and CD1c+ dendritic cells in vivo.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	O'Keeffe, Meredith Fancke, Ben Ding, Yitian Idris, Adi Lahoud, Mireille H. Vuckovic, Slavica Shortman, Ken Khalil, Dalia Ju, Xinsheng Wilkinson, Andrew Rodwell, Robyn Radford, Kristen J. Caminschi, Irina
Description	Author Affiliation: Ding Y ( Mater Research, Translational Research Institute, Brisbane, Queensland 4102, Australia)
Abstract	We established a humanized mouse model incorporating FLT3-ligand (FLT3-L) administration after hematopoietic cell reconstitution to investigate expansion, phenotype, and function of human dendritic cells (DC). FLT3-L increased numbers of human CD141(+) DC, CD1c(+) DC, and, to a lesser extent, plasmacytoid DC (pDC) in the blood, spleen, and bone marrow of humanized mice. CD1c(+) DC and CD141(+) DC subsets were expanded to a similar degree in blood and spleen, with a bias toward expansion of the CD1c(+) DC subset in the bone marrow. Importantly, the human DC subsets generated after FLT3-L treatment of humanized mice are phenotypically and functionally similar to their human blood counterparts. CD141(+) DC in humanized mice express C-type lectin-like receptor 9A, XCR1, CADM1, and TLR3 but lack TLR4 and TLR9. They are major producers of IFN-λ in response to polyinosinic-polycytidylic acid but are similar to CD1c(+) DC in their capacity to produce IL-12p70. Although all DC subsets in humanized mice are efficient at presenting peptide to CD8(+) T cells, CD141(+) DC are superior in their capacity to cross-present protein Ag to CD8(+) T cells following activation with polyinosinic-polycytidylic acid. CD141(+) DC can be targeted in vivo following injection of Abs against human DEC-205 or C-type lectin-like receptor 9A. This model provides a feasible and practical approach to dissect the function of human CD141(+) and CD1c(+) DC and evaluate adjuvants and DC-targeting strategies in vivo.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-02-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adjuvants, Immunologic Pharmacology Antigens, Cd1 Metabolism Antigens, Surface Dendritic Cells Drug Effects Immunology Glycoproteins Membrane Proteins Administration & Dosage Animals Antigen Presentation Antigens, Cd Cd8-positive T-lymphocytes Cell Adhesion Molecules Immunoglobulins Interferon-gamma Interleukin-12 Lectins, C-type Lymphocyte Activation Mice Mice, Inbred Nod Mice, Scid Minor Histocompatibility Antigens Poly I-c Receptors, Cell Surface Receptors, Chemokine Toll-like Receptor 3 Toll-like Receptor 4 Toll-like Receptor 9 Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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