Triiodothyronine (T3) Induces Limited Transcriptional and DNA Methylation Reprogramming in Human Monocytes
Thyroid hormones have immunomodulatory roles, but their effects on the transcriptome and epigenome of innate immune cell types remain unexplored. In this study, we investigate the effects of triiodothyronine (T3) on the transcriptome and methylome of human monocytes in vitro, both in resting and lip...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/3/608 |
| _version_ | 1827649913288130560 |
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| author | Rebecca Shepherd Bowon Kim Richard Saffery Boris Novakovic |
| author_facet | Rebecca Shepherd Bowon Kim Richard Saffery Boris Novakovic |
| author_sort | Rebecca Shepherd |
| collection | DOAJ |
| description | Thyroid hormones have immunomodulatory roles, but their effects on the transcriptome and epigenome of innate immune cell types remain unexplored. In this study, we investigate the effects of triiodothyronine (T3) on the transcriptome and methylome of human monocytes in vitro, both in resting and lipopolysaccharide (LPS)-stimulated conditions. In resting monocytes, 5 µM T3 affected the expression of a small number of monocyte-to-macrophage differentiation-associated genes, including <i>TLR4</i> (<i>p</i>-value < 0.05, expression fold change >1.5). T3 attenuated a small proportion of monocyte-to-macrophage differentiation-associated DNA methylation changes, while specifically inducing DNA methylation changes at several hundred differentially methylated CpG probes (DMPs) (<i>p</i>-value < 0.05, Δβ > 0.05). In LPS-stimulated monocytes, the presence of T3 attenuated the effect of 27% of LPS-induced DMPs (<i>p</i>-value < 0.05, Δβ > 0.05). Interestingly, co-stimulation with T3 + LPS induced a unique DNA methylation signature that was not observed in the LPS-only or T3-only exposure groups. Our results suggest that T3 induces limited transcriptional and DNA methylation remodeling in genes enriched in metabolism and immune processes and alters the normal in vitro LPS response. The overlap between differentially expressed genes and genes associated with DMPs was minimal; thus, other epigenetic mechanisms may underpin the expression changes. This research provides insight into the complex interplay between thyroid hormones, epigenetic remodeling, and transcriptional dynamics in monocytes. |
| first_indexed | 2024-03-09T20:06:14Z |
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| id | doaj.art-cfecb86ddbb841e1b8406016f87c4366 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T20:06:14Z |
| publishDate | 2022-03-01 |
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| spelling | doaj.art-cfecb86ddbb841e1b8406016f87c43662023-11-24T00:32:42ZengMDPI AGBiomedicines2227-90592022-03-0110360810.3390/biomedicines10030608Triiodothyronine (T3) Induces Limited Transcriptional and DNA Methylation Reprogramming in Human MonocytesRebecca Shepherd0Bowon Kim1Richard Saffery2Boris Novakovic3Molecular Immunity, Infection and Immunity Theme, Murdoch Children’s Research Institute, Parkville, VIC 3052, AustraliaMolecular Immunity, Infection and Immunity Theme, Murdoch Children’s Research Institute, Parkville, VIC 3052, AustraliaMolecular Immunity, Infection and Immunity Theme, Murdoch Children’s Research Institute, Parkville, VIC 3052, AustraliaMolecular Immunity, Infection and Immunity Theme, Murdoch Children’s Research Institute, Parkville, VIC 3052, AustraliaThyroid hormones have immunomodulatory roles, but their effects on the transcriptome and epigenome of innate immune cell types remain unexplored. In this study, we investigate the effects of triiodothyronine (T3) on the transcriptome and methylome of human monocytes in vitro, both in resting and lipopolysaccharide (LPS)-stimulated conditions. In resting monocytes, 5 µM T3 affected the expression of a small number of monocyte-to-macrophage differentiation-associated genes, including <i>TLR4</i> (<i>p</i>-value < 0.05, expression fold change >1.5). T3 attenuated a small proportion of monocyte-to-macrophage differentiation-associated DNA methylation changes, while specifically inducing DNA methylation changes at several hundred differentially methylated CpG probes (DMPs) (<i>p</i>-value < 0.05, Δβ > 0.05). In LPS-stimulated monocytes, the presence of T3 attenuated the effect of 27% of LPS-induced DMPs (<i>p</i>-value < 0.05, Δβ > 0.05). Interestingly, co-stimulation with T3 + LPS induced a unique DNA methylation signature that was not observed in the LPS-only or T3-only exposure groups. Our results suggest that T3 induces limited transcriptional and DNA methylation remodeling in genes enriched in metabolism and immune processes and alters the normal in vitro LPS response. The overlap between differentially expressed genes and genes associated with DMPs was minimal; thus, other epigenetic mechanisms may underpin the expression changes. This research provides insight into the complex interplay between thyroid hormones, epigenetic remodeling, and transcriptional dynamics in monocytes.https://www.mdpi.com/2227-9059/10/3/608monocytesthyroid hormoneT3triiodothyronineDNA methylationtranscriptome |
| spellingShingle | Rebecca Shepherd Bowon Kim Richard Saffery Boris Novakovic Triiodothyronine (T3) Induces Limited Transcriptional and DNA Methylation Reprogramming in Human Monocytes Biomedicines monocytes thyroid hormone T3 triiodothyronine DNA methylation transcriptome |
| title | Triiodothyronine (T3) Induces Limited Transcriptional and DNA Methylation Reprogramming in Human Monocytes |
| title_full | Triiodothyronine (T3) Induces Limited Transcriptional and DNA Methylation Reprogramming in Human Monocytes |
| title_fullStr | Triiodothyronine (T3) Induces Limited Transcriptional and DNA Methylation Reprogramming in Human Monocytes |
| title_full_unstemmed | Triiodothyronine (T3) Induces Limited Transcriptional and DNA Methylation Reprogramming in Human Monocytes |
| title_short | Triiodothyronine (T3) Induces Limited Transcriptional and DNA Methylation Reprogramming in Human Monocytes |
| title_sort | triiodothyronine t3 induces limited transcriptional and dna methylation reprogramming in human monocytes |
| topic | monocytes thyroid hormone T3 triiodothyronine DNA methylation transcriptome |
| url | https://www.mdpi.com/2227-9059/10/3/608 |
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