IL-10-conditioned dendritic cells, decommissioned for recruitment of adaptive immunity, elicit innate inflammatory gene products in response to danger signals.
Dendritic cells (DCs) are the professional APCs of the immune system, enabling T cells to perceive and respond appropriately to potentially dangerous microbes, while also being able to maintain T cell tolerance toward self. In part, such tolerance can be determined by IL-10 released from certain types of regulatory T cells. IL-10 has previously been shown to render DCs unable to activate T cells and it has been assumed that this process represents a general block in maturation. Using serial analysis of gene expression, we show that IL-10 pretreatment of murine bone marrow-derived DCs alone causes significant changes in gene expression. Furthermore, these cells retain the ability to respond to Toll-like receptor agonists, but in a manner skewed toward the selective induction of mediators known to enhance local inflammation and innate immunity, among which we highlight a novel CXCR2 ligand, DC inflammatory protein-1. These data suggest that, while the presence of a protolerogenic and purportedly anti-inflammatory agent such as IL-10 precludes DCs from acquiring their potential as initiators of adaptive immunity, their ability to act as initiators of innate immunity in response to Toll-like receptor signaling is enhanced.
Nolan
Kathleen F
KF
Sir William Dunn School of Pathology, Oxford University, Oxford, United Kingdom. kathleen.nolan@path.ox.ac.uk
Strong
Victoria
V
Soler
Dulce
D
Fairchild
Paul J
PJ
Cobbold
Stephen P
SP
Croxton
Ruth
R
Gonzalo
Jose-Angel
JA
Rubio
Ana
A
Wells
Meghan
M
Waldmann
Herman
H
D020816:Amino Acid Motifs; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D015723:Gene Library; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D020556:Neutrophil Infiltration / Q000276:immunology; D021141:Nucleic Acid Amplification Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D023063:Receptors, Interleukin-8B / Q000502:physiology
D019743:Chemokines, CXC; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D023063:Receptors, Interleukin-8B; C092499:Tgtp protein, mouse; D016753:Interleukin-10; D020559:Monomeric GTP-Binding Proteins