title: IL-10 deficiency blocks the ability of LPS to regulate expression of tolerance-related molecules on dendritic cells.
abstract: Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays an important role in regulating the local inflammatory immune response, but regulatory mechanisms of this cytokine have not been fully elucidated. Here, we demonstrate that IL-10 deficiency renders LPS treatment ineffective in regulating the expression of CD40, CD80, CD86, B7-H2, and B7-DC on dendritic cells (DCs) and blocks upregulation of IL-27. This inability to respond to LPS was found in both IL-10(-/-)  bone marrow derived and splenic DCs. Compared with wild-type DCs, IL-10(-/-)  DCs expressed similar levels of TLR4 and CD14, but produced less LPS-binding protein. The deficiency in LPS-binding protein production may explain the failure of IL-10(-/-)  DCs to respond normally to LPS. Moreover, lack of IL-10 modulated the proportions of CD11c(+) CD8(+)  and CD11c(+) B220(+)  DCs, which play an important role in local inflammatory responses and tolerance. IL-10 deficiency also blocked expression of galectin-1, CD205, and CD103, which are necessary for central and peripheral tolerance. While they did not respond to LPS, IL-10(-/-)  DCs produced increased levels of IL-6 and CCL4 after TNF-α treatment. Together, our results demonstrate that IL-10 deficiency affects the immune functions of DCs, which may contribute to the increased severity of autoimmune diseases seen in IL-10(-/-)  mice.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Bogoljub
authors.initials: B
authors.lastname: Ciric
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yan
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Melissa
authors.initials: M
authors.lastname: Cullimore
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Lauretti
authors.forename: Patricia
authors.initials: P
authors.lastname: Gonnella
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D002454:Cell Differentiation; D054407:Chemokine CCL4 / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D037483:Galectin 1 / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D039001:Integrin alpha Chains / Q000032:analysis; D016753:Interleukin-10 / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000032:analysis; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D015703:Antigens, CD; D002352:Carrier Proteins; D054407:Chemokine CCL4; D037483:Galectin 1; D000949:Histocompatibility Antigens Class II; D039001:Integrin alpha Chains; D016753:Interleukin-10; D015850:Interleukin-6; D007378:Interleukins; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D000099231:Lipopolysaccharide-Binding Protein; C408982:CPG-oligonucleotide; C093569:DEC-205 receptor; C486767:Il27 protein, mouse; C091367:alpha E integrins