Single-cell RNA sequencing uncovers heterogenous immune cell responses upon exposure to food additive (E171) titanium dioxide.

Autor: Perumalsamy H; Institute for Next Generation Material Design, Hanyang University, Seoul, 04763, Republic of Korea.; Research Institute for Convergence of Basic Science, Hanyang University, Seoul, 04763, South Korea.; Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Xiao X; Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea., Han HY; Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Republic of Korea., Oh JH; Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Republic of Korea., Yoon S; Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Republic of Korea., Heo MB; Nanosafety Metrology Center, Korea Research Institute of Standards and Science (KRISS), Daejeon, Republic of Korea., Lee TG; Nanosafety Metrology Center, Korea Research Institute of Standards and Science (KRISS), Daejeon, Republic of Korea., Kim HY; Institute for Next Generation Material Design, Hanyang University, Seoul, 04763, Republic of Korea.; Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea.; NGeneS Inc., Gyeonggi-do, 15495, Republic of Korea., Yoon TH; Institute for Next Generation Material Design, Hanyang University, Seoul, 04763, Republic of Korea. taeyoon@hanyang.ac.kr.; Research Institute for Convergence of Basic Science, Hanyang University, Seoul, 04763, South Korea. taeyoon@hanyang.ac.kr.; Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea. taeyoon@hanyang.ac.kr.; Department of Medical and Digital Engineering, Hanyang University, Seoul, 04763, Republic of Korea. taeyoon@hanyang.ac.kr.; Yoon Idea Lab. Co. Ltd, Seoul, 04763, Republic of Korea. taeyoon@hanyang.ac.kr.
Jazyk: angličtina
Zdroj: Journal of nanobiotechnology [J Nanobiotechnology] 2024 Dec 19; Vol. 22 (1), pp. 765. Date of Electronic Publication: 2024 Dec 19.
DOI: 10.1186/s12951-024-03036-9
Abstrakt: The prospective use of food additive titanium dioxide (E171 TiO 2 ) in a variety of fields (food, pharmaceutics, and cosmetics) prompts proper cellular cytotoxicity and transcriptomic assessment. Interestingly, smaller-sized E171 TiO 2 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 2 is yet to be elucidated. For this purpose, we have used male Sprague-Dawley rats to deliver E171 TiO 2 (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 2 .
Competing Interests: Declarations. Ethical approval and consent to participate: This study was approved by the Animal Welfare and Guide for the Care and Use of Laboratory Animals and was assessed by the Institutional Animal Care and Use Committee (IACUC) (approval number N221019). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE