Murine models of lupus induced by hypomethylated T cells - PubMed (original) (raw)

Murine models of lupus induced by hypomethylated T cells

Bruce Richardson et al. Methods Mol Med. 2004.

Abstract

CD4+ T-cell DNA hypomethylation may contribute to the development of drug-induced and idiopathic human lupus. Inhibiting DNA methylation in mature CD4+ T cells causes autoreactivity specific to the major histocompatibility complex in vitro. The lupus-inducing drugs hydralazine and procainamide also inhibit T-cell DNA methylation and induce autoreactivity, and T cells from patients with active lupus have hypomethylated DNA and a similarly autoreactive T-cell subset. Further, T cells treated with DNA methylation inhibitors demethylate the same sequences that demethylate in T cells from patients with active lupus. The pathological significance of the autoreactivity induced by inhibiting T-cell DNA methylation has been tested by treating murine T cells in vitro with drugs that modify DNA methylation, then injecting the cells into syngeneic female mice. Mice receiving CD4+ T cells demethylated by a variety of agents, including procainamide and hydralazine, develop a lupuslike disease. This chapter describes the protocols for inducing autoreactivity in murine T cells in vitro and using the cells to induce autoimmunity in vivo.

PubMed Disclaimer

Similar articles

• Murine models of lupus induced by hypomethylated T cells (DNA hypomethylation and lupus…).
  Richardson B, Sawalha AH, Ray D, Yung R. Richardson B, et al. Methods Mol Biol. 2012;900:169-80. doi: 10.1007/978-1-60761-720-4_8. Methods Mol Biol. 2012. PMID: 22933069
• Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice.
  Quddus J, Johnson KJ, Gavalchin J, Amento EP, Chrisp CE, Yung RL, Richardson BC. Quddus J, et al. J Clin Invest. 1993 Jul;92(1):38-53. doi: 10.1172/JCI116576. J Clin Invest. 1993. PMID: 7686923 Free PMC article.
• Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice.
  Yung R, Powers D, Johnson K, Amento E, Carr D, Laing T, Yang J, Chang S, Hemati N, Richardson B. Yung R, et al. J Clin Invest. 1996 Jun 15;97(12):2866-71. doi: 10.1172/JCI118743. J Clin Invest. 1996. PMID: 8675699 Free PMC article.
• DNA methylation in T cells from idiopathic lupus and drug-induced lupus patients.
  Zhou Y, Lu Q. Zhou Y, et al. Autoimmun Rev. 2008 May;7(5):376-83. doi: 10.1016/j.autrev.2008.03.003. Epub 2008 Apr 4. Autoimmun Rev. 2008. PMID: 18486925 Review.
• Role of T cell DNA methylation in lupus syndromes.
  Yung RL, Richardson BC. Yung RL, et al. Lupus. 1994 Dec;3(6):487-91. doi: 10.1177/096120339400300611. Lupus. 1994. PMID: 7535621 Review.

Cited by

• Monocyte enhancers are highly altered in systemic lupus erythematosus.
  Shi L, Zhang Z, Song L, Leung YT, Petri MA, Sullivan KE. Shi L, et al. Epigenomics. 2015;7(6):921-35. doi: 10.2217/epi.15.47. Epub 2015 Oct 7. Epigenomics. 2015. PMID: 26442457 Free PMC article.
• Epigenetic Aspects of Systemic Lupus Erythematosus.
  Relle M, Foehr B, Schwarting A. Relle M, et al. Rheumatol Ther. 2015 Jun;2(1):33-46. doi: 10.1007/s40744-015-0014-y. Epub 2015 Jun 16. Rheumatol Ther. 2015. PMID: 27747498 Free PMC article. Review.
• New insights into the immunopathogenesis of systemic lupus erythematosus.
  Tsokos GC, Lo MS, Costa Reis P, Sullivan KE. Tsokos GC, et al. Nat Rev Rheumatol. 2016 Nov 22;12(12):716-730. doi: 10.1038/nrrheum.2016.186. Nat Rev Rheumatol. 2016. PMID: 27872476 Review.
• Hirsutella sinensis mycelium regulates autophagy of alveolar macrophages via TLR4/NF-κB signaling pathway.
  Fu J, Lu L, Wang H, Hou Y, Dou H. Fu J, et al. Int J Med Sci. 2021 Feb 18;18(8):1810-1823. doi: 10.7150/ijms.51654. eCollection 2021. Int J Med Sci. 2021. PMID: 33746598 Free PMC article.
• Lupus, DNA Methylation, and Air Pollution: A Malicious Triad.
  Rasking L, Roelens C, Sprangers B, Thienpont B, Nawrot TS, De Vusser K. Rasking L, et al. Int J Environ Res Public Health. 2022 Nov 15;19(22):15050. doi: 10.3390/ijerph192215050. Int J Environ Res Public Health. 2022. PMID: 36429769 Free PMC article. Review.

References

1. 1. Attwood JT, Yung RL, Richardson BC. DNA methylation and the regulation of gene transcription. Cell Mol Life Sci. 2002;59:241–57. - PMC - PubMed
2. 1. Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 1992;69:915–26. - PubMed
3. 1. Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99:247–57. - PubMed
4. 1. Taylor SM, Jones PA. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell. 1979;17:771–9. - PubMed
5. 1. Golbus J, Palella TD, Richardson BC. Quantitative changes in T cell DNA methylation occur during differentiation and ageing. Eur J Immunol. 1990;20:1869–72. - PubMed

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Europe PubMed Central
  • PubMed Central

• Medical

  • MedlinePlus Health Information

• Research Materials

  • NCI CPTC Antibody Characterization Program