Human 6-sulfo LacNAc-expressing dendritic cells are principal producers of early interleukin-12 and are controlled by erythrocytes.
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.
Schäkel
Knut
K
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: knut.schaekel@tu-dresden.de.
von Kietzell
Matthias
M
Institute of Immunology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany.
Hänsel
Anja
A
Institute of Immunology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany.
Ebling
Annette
A
Institute of Immunology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany.
Schulze
Livia
L
Institute of Immunology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany.
Haase
Michael
M
Institute of Pathology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany.
Semmler
Christian
C
Department of Dermatology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany.
Sarfati
Marika
M
Centre Hospitalier de l'Universite de Montreal Research Center, Hospital Notre-Dame, Montreal, Quebec H2L 4M1, Canada.
Barclay
A Neil
AN
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Randolph
Gwendalyn J
GJ
Department of Gene and Cell Medicine, Icahn Research Institute, Mount Sinai School of Medicine, New York, New York 10029.
Meurer
Michael
M
Department of Dermatology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany.
Rieber
E Peter
EP
Institute of Immunology, OncoRay, Biological and Molecular Targeting, Medical Faculty, Technische Universität Dresden, 01307 Dresden, Germany.
D000606:Amino Sugars; D000943:Antigens, Differentiation / Q000032:analysis / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D023201:CD40 Ligand / Q000494:pharmacology; D051928:CD47 Antigen / Q000032:analysis / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology; D011565:Psoriasis / Q000276:immunology / Q000473:pathology; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists
C467438:6-sulfo-LacNac; D000606:Amino Sugars; D000943:Antigens, Differentiation; D051928:CD47 Antigen; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D023201:CD40 Ligand; D018664:Interleukin-12