Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Briefing
  • Published:

Human regulatory T cells turn into cytotoxic ‘exTreg’ cells in atherosclerosis

That regulatory T cells can change their phenotypes has been shown in mouse models of atherosclerosis and other autoimmune diseases. We suspected that this phenomenon would also be true in humans. To test this hypothesis, we developed a strategy to identify human ‘exTreg’ cells and found that they express a cytotoxic transcriptome.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Deep transcriptomes from sorted human CD3+CD4+CD16+CD56+ exTreg and Treg cells.

References

  1. Wolf, D. et al. Pathogenic autoimmunity in atherosclerosis evolves from initially protective apolipoprotein B100-reactive CD4+ T-regulatory cells. Circulation 142, 1279–1293 (2020). This paper shows how the transcriptomes of CD4+ T cells that recognize an atherosclerosis-specific antigen diverge from Treg cell transcriptomes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Butcher, M. J. et al. atherosclerosis-driven treg plasticity results in formation of a dysfunctional subset of plastic IFNγ+ Th1/Tregs. Circ Res. 119, 1190–1203 (2016). This paper identified T helper 1-like exTreg cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Saigusa, R. et al. Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease. Nat. Cardiovasc. Res. 1, 462–475 (2022). This paper shows that adoptive transfer of exTreg cells into mice increases producion of the pro-inflammatory cytokine IFNγ.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bailey-Bucktrout, S. L. et al. Self-antigen-driven activation induces instability of regulatory T cells during an inflammatory autoimmune response. Immunity 39, 949–962 (2013). This paper first showed that only antigen-specific Treg cells become exTreg cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sharma, M. D. et al. Reprogrammed Foxp3+ regulatory T cells provide essential help to support cross-presentation and CD8+ T cell priming in naive mice. Immunity 33, 942–954 (2010). This paper shows that Treg cells can evolve to help control cancer in mice.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Freuchet, A. et al. Identification of human exTreg cells as CD16+CD56+ cytotoxic CD4+ T cells. Nat. Immunol. https://doi.org/10.1038/s41590-023-01589-9 (2023).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Human regulatory T cells turn into cytotoxic ‘exTreg’ cells in atherosclerosis. Nat Immunol 24, 1614–1615 (2023). https://doi.org/10.1038/s41590-023-01629-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41590-023-01629-4

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing