title: Resident and monocyte-derived dendritic cells become dominant IL-12 producers under different conditions and signaling pathways.
abstract: IL-12 is such a pivotal cytokine that it has been called the third signal for T cell activation, TCR engagement being the first and costimulation being the second. It has been generally viewed that the resident CD8(+) dendritic cell (DC) subset is the predominant IL-12-producing cell type. In this study, we found, although this is so under steady state conditions, under inflammatory conditions monocyte-derived DC (mDC) became a major cell type producing IL-12. Depletion of either type of DC resulted in reduced production of IL-12 in vivo. For CD8(+) DC, IL-12 production could be stimulated by various pathways viz. signaling through MyD88, Trif, or nucleotide-binding oligomerization domain (Nod)-like receptors. In contrast, for mDC, IL-12 production was mainly dependent on MyD88 signaling. Thus, conventional DCs and mDCs use different pathways to regulate IL-12 production.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. zhan@wehi.edu.au
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhan
authors.forename: Yuekang
authors.initials: Y
authors.lastname: Xu
authors.forename: Shirley
authors.initials: S
authors.lastname: Seah
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Brady
authors.forename: Emma M
authors.initials: EM
authors.lastname: Carrington
authors.forename: Christina
authors.initials: C
authors.lastname: Cheers
authors.forename: Ben A
authors.initials: BA
authors.lastname: Croker
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Jose A
authors.initials: JA
authors.lastname: Villadangos
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000119:Acetylmuramyl-Alanyl-Isoglutamine; D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; D018664:Interleukin-12; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D053473:Nod2 Signaling Adaptor Protein; D011070:Poly I-C; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; C507780:Myd88 protein, mouse; C495945:Nod2 protein, mouse; C476286:Ticam1 protein, mouse; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse