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IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis.

ABSTRACT: Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of cytokines and chemokines were detected by microarray, real-time PCR, ELISA and multiple colors flow cytometry. Adoptive transfer of macrophages and imiquimod-induced psoriasis mice were used. In contrast to M1- and M2-polarized macrophages, IL-23-treated macrophages produce large amounts of IL-17A, IL-22 and IFN-?. Biochemical and molecular studies showed that IL-23 induces IL-17A expression in macrophages through the signal transducer and activator of transcription 3 (STAT3)-retinoid related orphan receptor-? T (ROR?T) pathway. T-bet mediates the IFN-? production in IL-23-treated macrophages. Importantly, IL-23-treated macrophages significantly promote the dermatitis pathogenesis in a psoriasis-like mouse model. IL-23-treated resting macrophages express a distinctive gene expression prolife compared with M1 and M2 macrophages. The identification of IL-23-induced macrophage polarization may help us to understand the contribution of macrophage subpopulation in Th17-cytokines-related pathogenesis.

SUBMITTER: Hou Y

PROVIDER: S-EPMC6251802 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis.

Hou Yuzhu Y Zhu Linnan L Tian Hongling H Sun Hai-Xi HX Wang Ruoyu R Zhang Lianfeng L Zhao Yong Y

Protein & cell 20180305 12

Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of c ...[more]

PMID: 29508278

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Project description:BackgroundThe polyphenol resveratrol has anti-inflammatory effects in various cells, tissues, animals and human settings of low-grade inflammation. Psoriasis is a disease of both localized and systemic low-grade inflammation. The Sirtuin1 enzyme thought to mediate the effects of resveratrol is present in skin and resveratrol is known to down regulate NF-κB; an important contributor in the development of psoriasis. Consequently we investigated whether resveratrol has an effect on an Imiquimod induced psoriasis-like skin inflammation in mice and sought to identify candidate genes, pathways and interleukins mediating the effects.MethodsThe study consisted of three treatment groups: A control group, an Imiquimod group and an Imiquimod+resveratrol group. Psoriasis severity was assessed using elements of the Psoriasis Area Severity Index, skin thickness measurements, and histological examination. We performed an RNA microarray from lesional skin and afterwards Ingenuity pathway analysis to identify affected signalling pathways. Our microarray was compared to a previously deposited microarray to determine if gene changes were psoriasis-like, and to a human microarray to determine if findings could be relevant in a human setting.ResultsImiquimod treatment induced a psoriasis-like skin inflammation. Resveratrol significantly diminished the severity of the psoriasis-like skin inflammation. The RNA microarray revealed a psoriasis-like gene expression-profile in the Imiquimod treated group, and highlighted several resveratrol dependent changes in relevant genes, such as increased expression of genes associated with retinoic acid stimulation and reduced expression of genes involved in IL-17 dependent pathways. Quantitative PCR confirmed a resveratrol dependent decrease in mRNA levels of IL-17A and IL-19; both central in developing psoriasis.ConclusionsResveratrol ameliorates psoriasis, and changes expression of retinoic acid stimulated genes, IL-17 signalling pathways, IL-17A and IL-19 mRNA levels in a beneficial manner, which suggests resveratrol, might have a role in the treatment of psoriasis and should be explored further in a human setting.

Project description:The experiments were done using an Orbitrap Fusion or an Orbitrap Fusion Lumos mass spectrometer. Multiplexing was achieved using either TMT10 or TMT11 reagents and the SPS-MS3 method. Basic pH reversed-phase chromatography (bRPLC) was used for off-line pre-fractionation; 12 fractions were analyzed for proteome mappings (PMID: 26700037) and 24 fractions plus a phosphotyrosine-enriched sample for phosphoproteome mappings (PMID: 31606085). Phosphoproteome mappings were done using both HCD fragmentation with Orbitrap fragment ion detection and CID fragmentation with ion trap fragment ion detection (PMID: 29487189, PMID: 31606085). If multiple TMT sets were required to analyze all samples from an experiment two bridge channels pooled from all samples was used to connect the data from the individual TMT sets (PMID: 28892078). Five proteomics experiments are described in the paper: (i) 1. Quantitative proteomics of fully polarized macrophages after 4 days of treatment with IL4 or IFNgamma/LPS to determine global proteome landscape of fully polarized THP-1-derived M1-type versus M2a-type macrophages: Proteome mapping on Orbitrap Fusion (one TMT set) RAW files: Marneros_4DayTreatment_proteome_fraction01 to ...fraction12 8 samples Labeling: PMA.1 (126), PMA.2 (127n), IL4.1 (127c), IL4.2 (128n), ILJQ1.1 (128c), ILJQ1.2 (129n), IFNgamma.1 (129c), IFNgamma.2 (130n) (ii) Time-course quantitative proteomics during the first 24 hours after induction of macrophage polarization in THP-1-derived macrophages to identify protein changes associated with M1-type (IFNgamma/LPS-induced) versus M2a-type (IL-4-induced) polarization: Proteome mapping on Orbitrap Fusion (three TMT sets: set01, set02, set03) RAW files: Marneros_timecourse_proteome_TMTset01_fraction01 to ...fraction12 Marneros_timecourse_proteome_TMTset02_fraction01 to ...fraction12 Marneros_timecourse_proteome_TMTset03_fraction01 to ...fraction12 22 samples Labeling: set01; bridge 1 (126), PMA 0min (127n), PMA 10min (127c), PMA 30min (128n), PMA 1h (128c), PMA 2h (129n), PMA 4h (129c), PMA 8h (130n), PMA 24h (130c), bridge 2 (131n) set02; bridge 1 (126), IL4 10min (127n), IL4 30min (127c), IL4 1h (128n), IL4 2h (128c), IL4 4h (129n), IL4 8h (129c), IL4 24h (130n), IFN 10min (130c), bridge 2 (131n) set03; bridge 1 (126), IFN 30min (127n), IFN 1h (127c), IFN 2h (128n), IFN 4h (128c), IFN 8h (129n), IFN 24h (129c), bridge 2 (131n) (iii) Time-course quantitative phosphoproteomics during the first 24 hours after induction of macrophage polarization in THP-1-derived macrophages to identify phosphorylation events associated with M1-type (IFNgamma/LPS-induced) versus M2a-type (IL-4-induced) polarization (same time points as in group 2): Phosphoproteome mapping on Orbitrap Fusion (three TMT sets: set01, set02, set03) RAW files: Marneros_timecourse_phospho_TMTset01_fraction01 to ...fraction06, ...fraction08 to ...fraction24, ...pY Marneros_timecourse_phospho_TMTset02_fraction01 to ...fraction12, ...fraction16 to ...fraction24, ...pY Marneros_timecourse_phospho_TMTset03_fraction01 to ...fraction24, ...pY The following RAW files gave no phosphopeptide quantifications (they are no included in the group of provided RAW files): set01_fraction07, set02_fraction13, set02_fraction14, set02_fraction15. 22 samples Labeling: as in (ii) (iv) Quantitative proteomics to assess the effects of the B-Raf inhibitor GDC-0879 or of the MEK inhibitor trametinib on IL-4-induced M2-type polarization and IFNgamma/LPS-induced M1-type polarization on THP-1-derived macrophages after 24 hours of treatment: Proteome mapping on Orbitrap Fusion (one TMT set) RAW files: Marneros_BRAF_inhibitor_proteine_fraction01 to ...fraction12 11 samples Labeling: IL4 1 (131c), IL4 2 (127n), IL4+GDC 1 (131n), IL4+GDC 2 (128n), IL4+TRAM 1 (130c), IL4+TRAM 2 (129n), IFNgamma+LPS 1 (130n), IFNgamma+LPS 2 (127c), IFNgamma+LPS+TRAM 1 (126), IFNgamma+LPS+TRAM 2(129c), IFNgamma+LPS+GDC (128c) (v) Quantitative phosphoproteomics to assess the effects of the B-Raf inhibitor GDC-0879 on IL-4-induced M2-type polarization and IFNgamma/LPS-induced M1-type polarization on THP-1-derived macrophages after 24 hours of treatment: Phosphoproteome mapping on Orbitrap Fusion Lumos (one TMT set) RAW files: Marneros_BRAF_inhibitor_phospho_fraction01 to ...fraction24, ...pY 7 samples Labeling: IL4 1 (131c), IL4 2 (127n), IL4+GDC 1 (130n), IL4+GDC 2 (128n), IFNgamma+LPS 1 (128c), IFNgamma+LPS 2 (127c), IFNgamma+LPS+GDC (130c)

Dataset Information

IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis.

Publications

IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis.

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