Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals.

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Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals.

Patsouris, D, Li, P.P., Thapar, D., Chapman, J., Olefsky, J.M., Neels, J.G.

Journal		Cell Metab.
Species
Analytes Measured		GM-CSF , IL-10 , IL-12 p70 , IL-6 , Insulin , MCP-1 , Resistin
Matrix Tested		Serum, Tissue lysates

Year		2008
Volume		8
Page Numbers		301-9
Application		Cytokines and Chemokines

Abstract

Obese adipose tissue is characterized by infiltration of macrophages. We and others recently showed that a specific subset of macrophages is recruited to obese adipose and muscle tissue. This subset expresses CD11c and produces high levels of proinflammatory cytokines that are linked to the development of obesity-associated insulin resistance. Here, we used a conditional cell ablation system, based on transgenic expression of the diphtheria toxin receptor under the control of the CD11c promoter, to study the effects of depletion of CD11c+ cells in obese mouse models. Our results show that CD11c+ cell depletion results in rapid normalization of insulin sensitivity. Furthermore, CD11c+ cell ablation leads to a marked decrease in inflammatory markers, both locally and systemically, as reflected by gene expression and protein levels. Together, these results indicate that these CD11c+ cells are a potential therapeutic target for treatment of obesity-related insulin resistance and type II diabetes.

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V-PLEX Metabolic Panel 1 Canine Kit GIP (active), GLP-1 (active), Glucagon, Insulin \| Canine Multiplex		NEW
V-PLEX Human Insulin Kit Insulin \| Human, Non-human primate, Canine Singleplex		NEW
V-PLEX Custom Human Biomarkers 1 C-Peptide, Eotaxin, Eotaxin-3, GIP (active), GLP-1 (active), Glucagon, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, Insulin, IP-10, Leptin, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PP, TARC, TNF-α, TNF-β, TSLP, VEGF-A \| Human Multiplex		NEW
V-PLEX Custom Mouse Biomarkers IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-17A/F, IL-27p28/IL-30, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, TNF-α \| Mouse Multiplex		NEW
V-PLEX Custom NHP Biomarkers 1 C-Peptide, Eotaxin, Eotaxin-3, GIP (active), GLP-1 (active), Glucagon, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, Insulin, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PP, TARC, TNF-β, VEGF-A \| Non-human primate Multiplex		NEW
V-PLEX Mouse IL-6 Kit IL-6 \| Mouse Singleplex
V-PLEX Mouse IL-10 Kit IL-10 \| Mouse Singleplex
V-PLEX Mouse IL-12p70 Kit IL-12p70 \| Mouse Singleplex
V-PLEX Plus Mouse IL-12p70 Kit IL-12p70 \| Mouse Singleplex
V-PLEX Plus Mouse IL-6 Kit IL-6 \| Mouse Singleplex
V-PLEX Plus Mouse IL-10 Kit IL-10 \| Mouse Singleplex
V-PLEX Plus Proinflammatory Panel 1 Mouse Kit IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α \| Mouse Multiplex
V-PLEX Proinflammatory Panel 1 Mouse Kit IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α \| Mouse Multiplex
V-PLEX Chemokine Panel 1 (NHP) Gen. B Kit Eotaxin, Eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC \| Non-human primate Multiplex
V-PLEX NHP MCP-1 Gen. B Kit MCP-1 \| Non-human primate Singleplex
V-PLEX Plus Chemokine Panel 1 (NHP) Gen. B Kit Eotaxin, Eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC \| Non-human primate Multiplex
V-PLEX Plus NHP MCP-1 Gen. B Kit MCP-1 \| Non-human primate Singleplex
V-PLEX Chemokine Panel 1 (human) Gen. B Kit Eotaxin, Eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC \| Human Multiplex
V-PLEX Cytokine Panel 1 NHP Kit GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Non-human primate Multiplex
V-PLEX Plus Cytokine Panel 1 NHP Kit GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Non-human primate Multiplex
V-PLEX Human MCP-1 Gen. B Kit MCP-1 \| Human Singleplex
V-PLEX NHP GM-CSF Kit GM-CSF \| Non-human primate Singleplex
V-PLEX Plus NHP GM-CSF Kit GM-CSF \| Non-human primate Singleplex
V-PLEX NHP IL-6 Kit IL-6 \| Non-human primate Singleplex
V-PLEX NHP IL-10 Kit IL-10 \| Non-human primate Singleplex
V-PLEX Plus Chemokine Panel 1 (human) Gen. B Kit Eotaxin, Eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC \| Human Multiplex
V-PLEX Plus Human MCP-1 Gen. B Kit MCP-1 \| Human Singleplex
V-PLEX Plus NHP IL-6 Kit IL-6 \| Non-human primate Singleplex
V-PLEX Plus NHP IL-10 Kit IL-10 \| Non-human primate Singleplex
V-PLEX Plus Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Plus Proinflammatory Panel 1 NHP Kit IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Proinflammatory Panel 1 NHP Kit IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex
V-PLEX Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex
V-PLEX Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex
V-PLEX Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Plus Human IL-6 Kit IL-6 \| Human Singleplex
V-PLEX Human IL-6 Kit IL-6 \| Human Singleplex
V-PLEX Human IL-10 Kit IL-10 \| Human Singleplex
V-PLEX Plus Human IL-10 Kit IL-10 \| Human Singleplex
V-PLEX Human IL-12p70 Kit IL-12p70 \| Human Singleplex
V-PLEX Plus Human IL-12p70 Kit IL-12p70 \| Human Singleplex
V-PLEX Plus Human GM-CSF Kit GM-CSF \| Human Singleplex
V-PLEX Human GM-CSF Kit GM-CSF \| Human Singleplex
V-PLEX Proinflammatory Panel 1 Human Kit IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex
V-PLEX Plus Proinflammatory Panel 1 Human Kit IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex
V-PLEX Plus Human Proinflam. Panel II (4-Plex) IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex
V-PLEX Plus Human Proinflam. Panel I (4-Plex) IFN-γ, IL-1β, IL-6, TNF-α \| Human Multiplex
V-PLEX Plus Cytokine Panel 1 Human Kit GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Human Multiplex
V-PLEX Human Proinflammatory Panel II (4-Plex) IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex
V-PLEX Human Proinflammatory Panel I (4-Plex) IFN-γ, IL-1β, IL-6, TNF-α \| Human Multiplex
V-PLEX Cytokine Panel 1 Human Kit GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Human Multiplex
R-PLEX Rabbit IL-6 Assay IL-6 \| Rabbit Singleplex
R-PLEX Rabbit IL-6 Antibody Set IL-6 \| Rabbit
U-PLEX Diabetes Combo 2 (human) C-Peptide, GIP (total), GLP-1 (active), Glucagon, Insulin, Leptin, PYY (total) \| Human Multiplex
U-PLEX Biomarker Group 1 (NHP) Assays CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17F, IL-18, IL-22, IL-23, IP-10, I-TAC, MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, VEGF-A, YKL-40 \| Non-human primate Multiplex
U-PLEX Custom Biomarker Group 1 (human) Assays CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
U-PLEX Custom Biomarker Group 1 (mouse) Assays 6CKine/CCL21, BAFF, BCA-1/BLC, CD40/TNFRSF5, Eotaxin, EPO, GM-CSF, IFN-α, IFN-β, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, IP-10, KC/GRO, MCP-1, MCP-5/CCL12, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α, MMP-9 (total), NGAL/LCN2, RANTES, SDF-1α, TARC, TNF-α, TNF-RI, VEGF-A \| Mouse Multiplex
U-PLEX Custom Metabolic Group 1 (human) Assays BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
U-PLEX Custom Metabolic Group 1 (mouse) Assays BAFF, BCA-1/BLC, BDNF, CD40/TNFRSF5, C-Peptide, Eotaxin, EPO, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, IFN-α, IFN-β, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, Insulin, IP-10, KC/GRO, Leptin, MCP-1, MCP-5/CCL12, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α, MMP-9 (total), PYY (total), RANTES, TARC, TNF-α, VEGF-A \| Mouse Multiplex
U-PLEX Custom Metabolic Group 1 (rat) Assays BDNF, C-Peptide, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) \| Rat Multiplex
U-PLEX Custom Immuno-Oncology Group 1 (human) Assays 4-1BBL/TNFSF9, APRIL/TNFSF13, BAFF-R/TNFRSF13C, BCMA/TNFRSF17, BTLA, CD20, CD27, CD28, CD40/TNFRSF5, CD40L (soluble), CD80/B7-1, CD276/B7-H3, CTACK, CTLA-4, E-Cadherin, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, E-Selectin, Fas (soluble), FasL, FGF (basic), FLT3L, Fractalkine, Galectin-9, G-CSF, GITR/TNFRSF18, GITRL/TNFSF18, GM-CSF, gp130 (soluble), Granzyme A, Granzyme B, GRO-α, HAVCR1/KIM-1, HAVCR2/TIM-3, HVEM/TNFRSF14, I-309, ICOS, ICOS-L/B7-H2, IDO-1, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, LAG3, LIGHT/TNFSF14, MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIG, MIP-1α, MIP-1β, MIP-5, MMP-1, MMP-2, MMP-7, MMP-8 (total), MMP-9 (total), MMP-10 (total), Nectin-4, OX40/TNFRSF4, PD1 (epitope 1), PD1 (epitope 2), PDGF-B, PD-L1 (epitope 1), PD-L1 (epitope 2), PD-L2, Pentraxin 3, Perforin, PlGF, proMMP-8, proMMP-9, proMMP-10, P-Selectin, RAGE (soluble), RANKL/TNFSF11, RANTES, S100A12, TACI/TNFRSF13B, Tie-2, TIGIT, TLR1, TNF-α, TNF-β, TNF-RI, TNF-RII, TPO, TRAIL, TSLP, VEGF-A, VEGF-D, VEGFR-1/Flt-1, YKL-40 \| Human Multiplex
U-PLEX Alzheimer's Disease Combo 1 (human) Eotaxin, IL-1α, IL-12/IL-23p40, IL-16, IL-17A, MCP-1, MDC, MIF, SDF-1α, YKL-40 \| Human Multiplex
U-PLEX Multiple Sclerosis Combo 1 (human) CTACK, Fractalkine, GRO-α, IL-7, IL-12/IL-23p40, IP-10, MCP-1, MIP-1β, MIP-3α \| Human Multiplex
U-PLEX TBI Combo 1 (human) CD40L (soluble), Fractalkine, IFN-γ, IL-1β, IL-6, IL-18, MCP-1, RANKL/TNFSF11, TNF-α, VEGF-D \| Human Multiplex
U-PLEX Chemokine Combo (mouse) IP-10, KC/GRO, MCP-1, MIP-1α, MIP-1β, MIP-2, MIP-3α \| Mouse Multiplex
U-PLEX Chemokine Combo 1 (human) Eotaxin, Eotaxin-2, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-2, MCP-3, MCP-4, MDC, MIP-1α, MIP-1β, TARC \| Human Multiplex		NEW
U-PLEX Chemokine Combo 1 (mouse) IP-10, KC/GRO, MCP-1, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α \| Mouse Multiplex
U-PLEX Chemokine Combo 1 (NHP) Eotaxin, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC \| Non-human primate Multiplex		NEW
U-PLEX Cytokine Combo 1 (human) GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Human Multiplex		NEW
U-PLEX Cytokine Combo 1 (NHP) GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Non-human primate Multiplex		NEW
U-PLEX Macrophage M1 Combo 1 (human) IL-1β, IL-6, IL-12p70, IL-18, IL-23, IP-10, MCP-1, MIP-1α, TNF-α \| Human Multiplex
U-PLEX Macrophage M1 Combo 1 (mouse) IL-1β, IL-6, IL-12p70, IL-15, IL-23, IP-10, MCP-1, MIP-1α, TNF-α \| Mouse Multiplex
U-PLEX Macrophage M2 Combo 1 (human) Eotaxin-2, IL-4, IL-10, IL-13, M-CSF, MDC, TARC \| Human Multiplex
U-PLEX Macrophage M2 Combo 1 (mouse) IL-4, IL-10, IL-13, MDC, TARC \| Mouse Multiplex
U-PLEX Proinflam Combo 1 (human) IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex		NEW
U-PLEX Proinflam Combo 1 (mouse) IFN-γ, IL-1β, IL-2, IL-6, IL-10, IL-12p70, IL-17A, IP-10, MCP-1, TNF-α \| Mouse Multiplex
U-PLEX Proinflam Combo 1 (NHP) IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12/IL-23p40, TNF-α \| Non-human primate Multiplex		NEW
U-PLEX Proinflam Combo 2 (human) GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70 \| Human Multiplex		NEW
U-PLEX Proinflam Combo 3 (human) IFN-γ, IL-1β, IL-6, TNF-α \| Human Multiplex		NEW
U-PLEX Proinflam Combo 4 (human) IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex		NEW
U-PLEX T-Cell Combo (human) GM-CSF, IFN-γ, IL-2, IL-4, IL-9, IL-10, IL-13, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, MIP-3α, TNF-α \| Human Multiplex
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Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals.

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