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

doi:10.1016/j.immuni.2006.03.020

Human 6-sulfo LacNAc-expressing dendritic cells are principal producers of early interleukin-12 and are controlled by erythrocytes

Immunity. 2006 Jun;24(6):767-777. doi: 10.1016/j.immuni.2006.03.020.

Authors

Affiliations

¹ Institute of Immunology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany; Department of Dermatology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany. Electronic address: [email protected].
² Institute of Immunology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany.
³ Institute of Pathology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany.
⁴ Department of Dermatology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany.
⁵ Centre Hospitalier de l'Universite de Montreal Research Center, Hospital Notre-Dame, Montreal, Quebec H2L 4M1, Canada.
⁶ Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
⁷ Department of Gene and Cell Medicine, Icahn Research Institute, Mount Sinai School of Medicine, New York, New York 10029.

PMID: 16782032
DOI: 10.1016/j.immuni.2006.03.020

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 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Sugars
Antigens, Differentiation / analysis
Antigens, Differentiation / metabolism
Arthritis, Rheumatoid / immunology
Arthritis, Rheumatoid / pathology
CD40 Ligand / pharmacology
CD47 Antigen / analysis
CD47 Antigen / metabolism
Coculture Techniques
Dendritic Cells / drug effects
Dendritic Cells / immunology*
Erythrocytes / immunology*
Humans
Interleukin-12 / metabolism*
Ligands
Lipopolysaccharides / immunology*
Lipopolysaccharides / pharmacology
Membrane Glycoproteins / immunology
Psoriasis / immunology
Psoriasis / pathology
Receptors, Immunologic / analysis
Receptors, Immunologic / metabolism
Th1 Cells / immunology
Toll-Like Receptor 4 / agonists

Substances

6-sulfo-LacNac
Amino Sugars
Antigens, Differentiation
CD47 Antigen
Ligands
Lipopolysaccharides
Membrane Glycoproteins
P-selectin ligand protein
Receptors, Immunologic
SIRPA protein, human
TLR4 protein, human
Toll-Like Receptor 4
CD40 Ligand
Interleukin-12

Grants and funding

G0400808/MRC_/Medical Research Council/United Kingdom