Human 6-Sulfo LacNAc-Expressing Dendritic Cells Are Principal Producers of Early Interleukin-12 and Are Controlled by Erythrocytes

Knut Schäkel, Matthias von Kietzell, Anja Hänsel, Annette Ebling, Livia Schulze, Michael Haase, Christian Semmler, Marika Sarfati, A. Neil Barclay, Gwendalyn J. Randolph, Michael Meurer, E. Peter Rieber

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140 Scopus citations

Abstract

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 SIRPα on DC. While strictly controlled in the blood by erythrocytes, the high IL-12- and TNF-α-producing capacity of slanDC in tissues may be critical in fighting off pathogens; if uncontrolled, it may lead to adverse inflammatory reactions.

Original languageEnglish
Pages (from-to)767-777
Number of pages11
JournalImmunity
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

Keywords

  • CELLIMMUNO

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    Schäkel, K., von Kietzell, M., Hänsel, A., Ebling, A., Schulze, L., Haase, M., Semmler, C., Sarfati, M., Barclay, A. N., Randolph, G. J., Meurer, M., & Rieber, E. P. (2006). Human 6-Sulfo LacNAc-Expressing Dendritic Cells Are Principal Producers of Early Interleukin-12 and Are Controlled by Erythrocytes. Immunity, 24(6), 767-777. https://doi.org/10.1016/j.immuni.2006.03.020