title: IL-10-conditioned dendritic cells, decommissioned for recruitment of adaptive immunity, elicit innate inflammatory gene products in response to danger signals.
abstract: 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.
authors.affiliation: Sir William Dunn School of Pathology, Oxford University, Oxford, United Kingdom. kathleen.nolan@path.ox.ac.uk
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Nolan
authors.forename: Victoria
authors.initials: V
authors.lastname: Strong
authors.forename: Dulce
authors.initials: D
authors.lastname: Soler
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fairchild
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Cobbold
authors.forename: Ruth
authors.initials: R
authors.lastname: Croxton
authors.forename: Jose-Angel
authors.initials: JA
authors.lastname: Gonzalo
authors.forename: Ana
authors.initials: A
authors.lastname: Rubio
authors.forename: Meghan
authors.initials: M
authors.lastname: Wells
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
mesh_terms: 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
chemical_list: 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