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
. 2022 Jan;52(1):75-84.
doi: 10.1002/eji.202149318. Epub 2021 Oct 13.

Helios is a marker, not a driver, of human Treg stability

Avery J Lam  1   2 , Prakruti Uday  1   2 , Jana K Gillies  1   2 , Megan K Levings  1   2   3
Affiliations
Free article

Helios is a marker, not a driver, of human Treg stability

Avery J Lam et al. Eur J Immunol. 2022 Jan.
Free article

Abstract

Treg therapy holds promise as a potentially curative approach to establish immune tolerance in transplantation and autoimmune disease. An outstanding question is whether therapeutic Tregs have the potential to transdifferentiate into effector T-cells and, thus, exacerbate rather than suppress immune responses. In mice, the transcription factor Helios is thought to promote Treg lineage stability in a range of inflammatory contexts. In humans, the role of Helios in Tregs is less clear, in part, due to the inability to enrich and study subsets of Helios-positive versus Helios-negative Tregs. Using an in vitro expansion system, we found that loss of high Helios expression and emergence of an intermediate Helios (Heliosmid )-expressing population correlated with Treg destabilization. We used CRISPR/Cas9 to genetically ablate Helios expression in human naive or memory Tregs and found that Helios-KO and unedited Tregs were equivalent in their suppressive function and stability in inflammation. Thus, high Helios expression is a marker, but not a driver, of human Treg stability in vitro. These data highlight the importance of monitoring Helios expression in therapeutic Treg manufacturing and provide new insight into the biological function of this transcription factor in human T-cells.

Keywords: CRISPR-Cas9; Helios; Treg stability; cell therapy; regulatory T cells.

PubMed Disclaimer

References

    1. Dawson, N. A. J., Vent-Schmidt, J. and Levings, M. K., Engineered tolerance: Tailoring development, function, and antigen-specificity of regulatory T cells. Front Immunol. 2017. 8: 1460.
    1. Dominguez-Villar, M. and Hafler, D. A., Regulatory T cells in autoimmune disease. Nat Immunol. 2018. 19: 665-673.
    1. Thornton, A. M., Korty, P. E., Tran, D. Q., Wohlfert, E. A., Murray, P. E., Belkaid, Y. and Shevach, E. M., Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol. 2010. 184: 3433-3441.
    1. Getnet, D., Grosso, J. F., Goldberg, M. V., Harris, T. J., Yen, H.-R., Bruno, T. C., Durham, N. M. et al., A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells. Mol Immunol. 2010. 47: 1595-1600.
    1. Pratama, A., Schnell, A., Mathis, D. and Benoist, C., Developmental and cellular age direct conversion of CD4+ T cells into RORgamma+ or Helios+ colon Treg cells. J Exp Med. 2020. 217: e20190428.

Publication types

Substances

Grants and funding

LinkOut - more resources