TRIM33 deficiency in mature myeloid cells impairs resolution of colonic inflammation
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PROVIDER: PRJNA513468 | ENA |
REPOSITORIES: ENA
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Project description:Mature myeloid cells play a crucial role in the pathogenesis of Crohn disease (CD) but the molecular players that regulate their functions in CD are not fully characterized. Here we show that Trim33 mRNA level is decreased in CD patient’s blood monocytes and characterize TRIM33 functions in monocytes during dextran sulfate sodium (DSS) induced colitis. Mice deleted for trim33 only in mature myeloid cells (Trim33-/- mice) display an impaired resolution of colonic inflammation. This deficiency is associated with an increased number of blood and colon neutrophils and monocytes and a decreased number of colonic macrophages. In accordance, Trim33-/- monocytes are less competent that wild type monocytes for recruitment and differentiation into macrophages at the inflammatory site. Furthermore, during resolution of DSS-induced colitis, Trim33-/- colonic macrophages display an impaired M1/M2 switch and express a low level of membrane bound TNFα known to regulate resolution of inflammation. Altogether, these results show an important role of TRIM33 in monocytes/macrophages during the resolution of DSS-induced colonic inflammation and pinpoint TRIM33 as a novel Crohn disease biomarker and as a potential therapeutic target.
2019-07-26 | GSE124778 | GEO
Project description:BackgroundMature myeloid cells play a crucial role in Crohn's disease (CD) but the molecular players that regulate their functions in CD are not fully characterized. We and others have shown that TRIM33 is involved in the innate immune response and in the inflammatory response but TRIM33 role in intestinal inflammation is not known. In this study, we investigated the role of TRIM33 in myeloid cells during dextran sulfate sodium (DSS)-induced colitis.MethodsWe study the role of TRIM33 during DSS-induced colitis which mimics intestinal inflammation using mice deleted for Trim33 only in mature myeloid cells (Trim33-/- mice) FINDINGS: We first show that Trim33 mRNA level is decreased in CD patient's blood monocytes suggesting a role of TRIM33 in CD. Using Trim33-/- mice, we show that these mice display an impaired resolution of colonic inflammation with an increased number of blood and colon monocytes and a decreased number of colonic macrophages. Trim33-/- monocytes are less competent for recruitment and macrophage differentiation. Finally, during resolution of inflammation, Trim33-/- colonic macrophages display an impaired M1/M2 switch and express a low level of membrane-bound TNF that is associated with an increased number of colonic neutrophils.InterpretationOur study shows an important role of TRIM33 in monocytes/macrophages during DSS-induced colitis and suggests that the decreased expression of TRIM33 in CD patient's blood monocytes might not be a consequence but might be involved in CD progression. FUND: La Ligue contre le Cancer (équipe labelisée), INSERM, CEA, Université Paris-Diderot, Université Paris-Sud.
| S-EPMC6604767 | biostudies-literature
Project description:To get insight into TRIM33 functions, TRIM33 ChIP-seq was carried out in murine macrophage cell line (RAW) and in bone marrow-derived macrophages (BMDM). The results showed that, in addition to its role in hematopoietic differentiation, TRIM33 may modulate PU.1 transcriptional activity during macrophage development and/or activation.To characterize the role of TRIM33 in macrophages, we bred TRIM33fl/fl mice with Lyz-Cre mice where the Cre recombinase gene is under the regulatory sequences of the Lyz gene that is expressed only in mature myeloid cells. Bone marrow cells from LyzCre/Trim33+/+ mice and LyzCre/Trim33flox/flox mice were differentiated in macrophages and treated during 0h, 4h, 12h and 24h with LPS. Using ChIP-seq, we provide a link between TRIM33 binding and H3K4me3 spreading on inflammatory genes in macrophages. Chromatin immunoprecipitations of TRIM33 and H3K4Me3 followed by multiparallel sequencing performed in murine bone marrow-derived macrophages (BMDM).
2015-11-23 | E-GEOD-43654 | biostudies-arrayexpress
Project description:To get insight into TRIM33 functions, TRIM33 ChIP-seq was carried out in murine macrophage cell line (RAW) and in bone marrow-derived macrophages (BMDM). The results showed that, in addition to its role in hematopoietic differentiation, TRIM33 may modulate PU.1 transcriptional activity during macrophage development and/or activation.To characterize the role of TRIM33 in macrophages, we bred TRIM33fl/fl mice with Lyz-Cre mice where the Cre recombinase gene is under the regulatory sequences of the Lyz gene that is expressed only in mature myeloid cells. Bone marrow cells from LyzCre/Trim33+/+ mice and LyzCre/Trim33flox/flox mice were differentiated in macrophages and treated during 0h, 4h, 12h and 24h with LPS. Using ChIP-seq, we provide a link between TRIM33 binding and H3K4me3 spreading on inflammatory genes in macrophages.
2015-11-23 | GSE43654 | GEO
Project description:We have analysed transcriptomic changes of colonic macrophages due to TGFβR1 deficiency.
2017-02-28 | GSE84765 | GEO
Project description:We report the genome-wide binding of Trim33 in Th17 cells. We found that more than 90% of Trim33 binding regions was located in non-conding sequence, and therefore reflect the role of Trim33 as a trancriptional co-factor. Trim33 was found to accumulate on cis-regulatory regions of genes that regulate the function of Th17 cells such as Il17a, Ccr6 and Il10. This study provides a basis for the comprehensive understanding of Trim33-mediated regulation of Th17 cells.
2018-05-08 | GSE114119 | GEO
Project description:Adenosine impairs the proliferative capacity of terminally mature NK cells
| PRJEB22631 | ENA
Project description:In differentiated mouse ESCs, most of the nodal/activin responsive genes are dependent on both Smad4 and Trim33, some are solely dependent on Smad4, and some are dependent on Trim33. Ebs at Day2.5 from WT, Smad4 null, and Trim33 knock-down ESCs, were treated with activin or SB 431542 for 2 h.
2012-01-09 | E-GEOD-32903 | biostudies-arrayexpress
Project description:Transposable elements (TEs) have been active in the mammalian genome for hundreds of millions of years and each TE has had a distinct period of transpositional activity, followed by inactivation. Mice carrying reporter transgenes can be used to model transcriptional silencing at TEs. A mutagenesis screen for modifiers of epigenetic gene silencing produced a line with a null mutation in Trim33. Heterozygous mutants displayed increased expression of the reporter transgene. ChIP-seq of Trim33 in testis revealed 9,109 peaks, mostly at promoters, across the mouse genome. Trim33 was enriched at many RLTR10B elements that are among the youngest retrotransposons in the mouse genome. RNA-seq revealed that testis of mice haploinsufficient for Trim33 had altered expression of a small group of genes. The gene with the most significant increase, Nmnat3, was found to be transcribed from an upstream RLTR10B element. We show that Trim33 is involved in repressing RLTR10B elements in mouse testis. Examination of Trim33 binding using ChIP sequencing and the result of Trim33 haploinsufficiency using RNA sequencing, in mouse testis
2015-11-06 | E-GEOD-68617 | biostudies-arrayexpress
Project description:To get insight into lineage-specific TRIM33 functions, TRIM33 ChIP-seq was carried out in non-differentiated erythroid (MEL NI), differentiated erythroid (MEL I), immature myeloid (32D). In addition, we compared the genome-wide profiles of RNA PolII occupancy between wild-type bone marrow-derived macrophages (BMDM) and Trim33-/- BMDM activated with LPS.
2021-09-17 | GSE73448 | GEO