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Early and high-level production of IL-12 is crucial for effective immune responses against pathogens. Up until now, the cells providing this initial IL-12 have remained elusive. Here we show that a subset of human blood dendritic cells (DC) is the principal and primary source of IL-12p70 when blood leukocytes are stimulated with the TLR4-ligand LPS or with CD40-ligand. These so-called slanDC are characterized by the 6-sulfo LacNAc modification of PSGL-1, which is identified by the mAb M-DC8. The IL-12 response of slanDC requires a few hours of in vitro maturation, which is completely blocked in the presence of erythrocytes. This inhibition of maturation depends on the expression of CD47 on erythrocytes and of its ligand SIRPalpha on DC. While strictly controlled in the blood by erythrocytes, the high IL-12- and TNF-alpha-producing capacity of slanDC in tissues may be critical in fighting off pathogens; if uncontrolled, it may lead to adverse inflammatory reactions.

Original publication

DOI

10.1016/j.immuni.2006.03.020

Type

Journal article

Journal

Immunity

Publication Date

06/2006

Volume

24

Pages

767 - 777

Keywords

Amino Sugars, Antigens, CD47, Antigens, Differentiation, Arthritis, Rheumatoid, CD40 Ligand, Coculture Techniques, Dendritic Cells, Erythrocytes, Humans, Interleukin-12, Ligands, Lipopolysaccharides, Membrane Glycoproteins, Psoriasis, Receptors, Immunologic, Th1 Cells, Toll-Like Receptor 4