Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2020 Apr 1;130(4):1618-1621.
doi: 10.1172/JCI135713.

CoRESTed development of regulatory T cells

Luisa Morales-Nebreda  1 , Kathryn A Helmin  1 , Benjamin D Singer  1   2   3
Affiliations
Comment

CoRESTed development of regulatory T cells

Luisa Morales-Nebreda et al. J Clin Invest. .

Abstract

Tregs require specific epigenetic signatures to induce and maintain their suppressive function in the context of inflammation and cancer surveillance. In this issue of the JCI, Xiong and colleagues identify a critical role for the epigenetic repressor REST corepressor 1 (CoREST) in promoting Treg suppressive transcriptional and functional programs. Pharmacologic inhibition and genetic loss of CoREST in Tregs impaired organ allograft tolerance and unleashed antitumor immunity via epigenetic activation of effector T cell programs. We propose that exploiting epigenetic control mechanisms will further the translation of Treg-based therapeutics to target inflammatory and malignant disorders.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: BDS has a pending patent application: US patent 15/542,380, Compositions and Methods to Accelerate Resolution of Acute Lung Inflammation.

Figures

Figure 1
Figure 1. Pharmacologic and epigenome editing approaches to Treg immunotherapy.
(A) Epigenetic writers and erasers define the epigenetic landscape and control transcription. (B) Ex vivo modification using pharmacologic or epigenome editing to alter the epigenetic landscape could generate Tregs that are fitted to a particular clinical context. Th1 Tregs could be infused to treat malignant disorders, and highly suppressive Tregs could be infused to treat inflammatory disorders such as systemic lupus erythematosus, organ allograft rejection, or graft-versus-host disease. HAT, histone acetyltransferase; TET, ten-eleven translocase (DNA demethylase); KMT, lysine methyltransferase; KDM, lysine demethylase.
See this image and copyright information in PMC

Comment on

References

    1. Sakaguchi S, Mikami N, Wing JB, Tanaka A, Ichiyama K, Ohkura N. Regulatory T cells and human disease. Annu Rev Immunol [published online February 4, 2020]. https://doi.org/10.1146/annurev-immunol-042718-041717. - PubMed
    1. Singer BD, Chandel NS. Immunometabolism of pro-repair cells. J Clin Invest. 2019;129(7):2597–2607. doi: 10.1172/JCI124613. - DOI - PMC - PubMed
    1. Brunkow ME, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet. 2001;27(1):68–73. doi: 10.1038/83784. - DOI - PubMed
    1. Wildin RS, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001;27(1):18–20. doi: 10.1038/83707. - DOI - PubMed
    1. Valencia X, Yarboro C, Illei G, Lipsky PE. Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J Immunol. 2007;178(4):2579–2588. doi: 10.4049/jimmunol.178.4.2579. - DOI - PubMed

Substances