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| Main Authors: | , , , , , , , , |
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| Format: | Recurso digital |
| Language: | English |
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Zenodo
2024
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| Online Access: | https://doi.org/10.1186/s12951-024-03036-9 |
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| _version_ | 1866901230116143104 |
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| author | Perumalsamy, Haribalan Xiao, Xiao Han, Hyoung-Yun Oh, Jung-Hwa Yoon, Seokjoon Heo, Min Beom Lee, Tae Geol Kim, Hyun-Yi Yoon, Tae-Hyung |
| author_facet | Perumalsamy, Haribalan Xiao, Xiao Han, Hyoung-Yun Oh, Jung-Hwa Yoon, Seokjoon Heo, Min Beom Lee, Tae Geol Kim, Hyun-Yi Yoon, Tae-Hyung |
| contents | <p>The prospective use of food additive titanium dioxide (E171 TiO<sub>2</sub>) in a variety of fields (food, pharmaceutics, and cosmetics) prompts proper cellular cytotoxicity and transcriptomic assessment. Interestingly, smaller-sized E171 TiO<sub>2</sub> can translocate in bloodstream and induce a diverse immunological response by activating the immune system, which can be either pro-inflammatory or immune-suppressive. Nevertheless, their cellular or immunologic responses in a heterogeneous population of the immune system following exposure of food additive E171 TiO<sub>2</sub> is yet to be elucidated. For this purpose, we have used male Sprague-Dawley rats to deliver E171 TiO<sub>2</sub> (5 mg/kg bw per day) via non-invasive intratracheal instillation for 13 weeks. After the 4 weeks recovery period, 3 mL of blood samples from both treated and untreated groups were collected for scRNAseq analysis. Firstly, granulocyte G1 activated innate immune response through the upregulation of genes involved in pro-inflammatory cytokine mediated cytotoxicity. Whereas NK cells resulted in heterogeneity role depending on the subsets where NK1 significantly inhibited cytotoxicity, whereas NK2 and NK3 subsets activated pro-B cell population & inhibited T cell mediated cytotoxicity respectively. While NKT_1 activated innate inflammatory responses which was confirmed by cytotoxic CD8+ T killer cell suppression. Similarly, NKT_2 cells promote inflammatory response by releasing lytic granules and MHC-I complex inhibition to arrest cytotoxic T killer cell responses. Conversely, NKT_3 suppressed inflammatory response by release of anti-inflammatory cytokines suggesting the functional heterogeneity of NKT subset. The formation of MHC-I or MHC-II complexes with T-cell subsets resulted in neither B and T cell dysfunction nor cytotoxic T killer cell inhibition suppressing adaptive immune response. Overall, our research offers an innovative high-dimensional approach to reveal immunological and transcriptomic responses of each cell types at the single cell level in a complex heterogeneous cellular environment by reassuring a precise assessment of immunological response of E171 TiO<sub>2</sub>.</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_1186_s12951-024-03036-9 |
| institution | Zenodo |
| language | eng |
| publishDate | 2024 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Single-cell RNA sequencing uncovers heterogenous immune cell responses upon exposure to food additive (E171) titanium dioxide Perumalsamy, Haribalan Xiao, Xiao Han, Hyoung-Yun Oh, Jung-Hwa Yoon, Seokjoon Heo, Min Beom Lee, Tae Geol Kim, Hyun-Yi Yoon, Tae-Hyung <p>The prospective use of food additive titanium dioxide (E171 TiO<sub>2</sub>) in a variety of fields (food, pharmaceutics, and cosmetics) prompts proper cellular cytotoxicity and transcriptomic assessment. Interestingly, smaller-sized E171 TiO<sub>2</sub> can translocate in bloodstream and induce a diverse immunological response by activating the immune system, which can be either pro-inflammatory or immune-suppressive. Nevertheless, their cellular or immunologic responses in a heterogeneous population of the immune system following exposure of food additive E171 TiO<sub>2</sub> is yet to be elucidated. For this purpose, we have used male Sprague-Dawley rats to deliver E171 TiO<sub>2</sub> (5 mg/kg bw per day) via non-invasive intratracheal instillation for 13 weeks. After the 4 weeks recovery period, 3 mL of blood samples from both treated and untreated groups were collected for scRNAseq analysis. Firstly, granulocyte G1 activated innate immune response through the upregulation of genes involved in pro-inflammatory cytokine mediated cytotoxicity. Whereas NK cells resulted in heterogeneity role depending on the subsets where NK1 significantly inhibited cytotoxicity, whereas NK2 and NK3 subsets activated pro-B cell population & inhibited T cell mediated cytotoxicity respectively. While NKT_1 activated innate inflammatory responses which was confirmed by cytotoxic CD8+ T killer cell suppression. Similarly, NKT_2 cells promote inflammatory response by releasing lytic granules and MHC-I complex inhibition to arrest cytotoxic T killer cell responses. Conversely, NKT_3 suppressed inflammatory response by release of anti-inflammatory cytokines suggesting the functional heterogeneity of NKT subset. The formation of MHC-I or MHC-II complexes with T-cell subsets resulted in neither B and T cell dysfunction nor cytotoxic T killer cell inhibition suppressing adaptive immune response. Overall, our research offers an innovative high-dimensional approach to reveal immunological and transcriptomic responses of each cell types at the single cell level in a complex heterogeneous cellular environment by reassuring a precise assessment of immunological response of E171 TiO<sub>2</sub>.</p> |
| title | Single-cell RNA sequencing uncovers heterogenous immune cell responses upon exposure to food additive (E171) titanium dioxide |
| url | https://doi.org/10.1186/s12951-024-03036-9 |