Effects of Lsd1 on the development and activation of regulatory T cells in mice

doi:10.3969/j.issn.1006-7795.2023.06.016

Abstract

Abstract: Objective To investigate the effects of lysine-specific demethylase 1 (Lsd1) in the development and activation of regulatory T cells (Treg). Methods Thymi, spleens, and lymph nodes were isolated from control and T cell-specific Lsd1 conditional knockout (Lsd1^fl/flLck-Cre) mice. The numbers and proportions of Tregs and the ratio changes of eTreg/cTreg were measured by flow cytometry. Results Compared with the control mice, the thymus indices and numbers of thymic CD4⁺ T cells decreased in the Lsd1 knockout mice, but the numbers and proportions of thymic Treg increased. In the spleen and lymph nodes, the proportions of Treg increased, so did the eTreg/cTreg ratio. Conclusion Conditional knockout of Lsd1 in T cells promotes the development of Tregs in the thymus and the activation of Tregs in the spleen and lymph nodes.

Key words: histone demethylase, lysine-specific demethylase 1, thymic atrophy, regulatory T cells

CLC Number:

R392

Xia Miaoran, Zhou Hang, Wang Dayi, Chen Ping. Effects of Lsd1 on the development and activation of regulatory T cells in mice[J]. Journal of Capital Medical University, 2023, 44(6): 1006-1013.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2023.06.016

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2023/V44/I6/1006

References

［1］Savage P A, Klawon D E J, Miller C H. Regulatory T cell development［J］. Annu Rev Immunol, 2020, 38： 421－453.
［2］Chen W J, Jin W W, Hardegen N, et al. Conversion of peripheral CD4⁺CD25^－ naive T cells to CD4⁺CD25⁺regulatory T cells by TGF-β induction of transcription factor Foxp3［J］. J Exp Med, 2003, 198(12)： 1875－1886.
［3］Levine A G, Arvey A, Jin W, et al. Continuous requirement for the TCR in regulatory T cell function［J］. Nat Immunol, 2014, 15(11)： 1070－1078.
［4］Smigiel K S, Richards E, Srivastava S, et al. CCR7 provides localized access to IL-2 and defines homeostatically distinct regulatory T cell subsets［J］. J Exp Med, 2014, 211(1)： 121－136.
［5］Vahl J C, Drees C, Heger K, et al. Continuous T cell receptor signals maintain a functional regulatory T cell pool［J］. Immunity, 2014, 41(5)： 722－736.
［6］Lee W, Lee G R. Transcriptional regulation and development of regulatory T cells［J］. Exp Mol Med, 2018, 50(3)： e456.
［7］ de Brito C B, Patra A K. NFAT factors are dispensable for the development but are critical for the maintenance of Foxp3⁺ regulatory T cells［J］. Cells, 2022, 11(9)： 1397.
［8］Hövelmeyer N, Schmidt-supprian M, Ohnmacht C. NF-κB in control of regulatory T cell development, identity, and function［J］. J Mol Med (Berl), 2022, 100(7)： 985－995.
［9］Ono M. Control of regulatory T-cell differentiation and function by T-cell receptor signalling and Foxp3 transcription factor complexes［J］. Immunology, 2020, 160(1)： 24－37.
［10］Shi Y J, Lan F, Matson C, et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1［J］. Cell, 2004, 119(7)： 941－953.
［11］Qin X K, Du Y, Liu X H, et al. LSD1 promotes prostate cancer cell survival by destabilizing FBXW7 at post-translational level［J］. Front Oncol, 2020, 10： 616185.
［12］Hu X, Xiang D X, Xie Y, et al. LSD1 suppresses invasion, migration and metastasis of luminal breast cancer cells via activation of GATA3 and repression of TRIM37 expression［J］. Oncogene, 2019, 38(44)： 7017－7034.
［13］Hong Y N, Li X F, Zhu J F. LSD1-mediated stabilization of SEPT6 protein activates the TGF－β1 pathway and regulates non-small-cell lung cancer metastasis［J］. Cancer Gene Ther, 2022, 29(2)： 189－201.
［14］Fang Y, Liao G C, Yu B. LSD1/KDM1A inhibitors in clinical trials： advances and prospects［J］. J Hematol Oncol, 2019, 12(1)： 129.
［15］Stamos D B, Clubb L M, Mitra A, et al. The histone demethylase Lsd1 regulates multiple repressive gene programs during T cell development［J］. J Exp Med, 2021, 218(12)： e20202012.
［16］Liu Y, Debo B, Li M F, et al. LSD1 inhibition sustains T cell invigoration with a durable response to PD-1 blockade［J］. Nat Commun, 2021, 12(1)： 6831.
［17］Kerenyi M A, Shao Z, Hsu Y J, et al. Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation［J］. Elife, 2013, 2： e00633.
［18］Lee P P, Fitzpatrick D R, Beard C, et al. A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival［J］. Immunity, 2001, 15(5)： 763－774.
［19］Li M O, Rudensky A Y. T cell receptor signalling in the control of regulatory T cell differentiation and function［J］. Nat Rev Immunol, 2016, 16(4)： 220－233.
［20］Xiong Y, Wang L Q, Di Giorgio E, et al. Inhibiting the coregulator CoREST impairs Foxp3+ Treg function and promotes antitumor immunity［J］. J Clin Invest, 2020, 130(4)： 1830－1842.
［21］Song Y, Dagil L, Fairall L, et al. Mechanism of crosstalk between the LSD1 demethylase and HDAC1 deacetylase in the CoREST complex［J］. Cell Rep, 2020, 30(8)： 2699－2711.e8.
［22］Sakaguchi S, Yamaguchi T, Nomura T, et al. Regulatory T cells and immune tolerance［J］. Cell, 2008, 133(5)： 775－787.
［23］Liu W, Fan J B, Xu D W, et al. Knockdown of LSD1 ameliorates the severity of rheumatoid arthritis and decreases the function of CD4 T cells in mouse models［J］. Int J Clin Exp Pathol, 2018, 11(1)： 333－341.

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