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T cells

Neuropilin 1 — distinguishing TReg cell subsets

Nature Reviews Immunology volume 12, pages 746–747 (2012)Cite this article

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Recombinase activating gene (RAG)-deficient mice that express certain transgenic T cell receptors (TCRs) fail to develop natural TReg cells. Yadav et al. and Weiss et al. used these mice to isolate induced TReg cells, and gene expression analyses of these cells revealed that they had low expression levels of the surface protein NRP1. Moreover, the FOXP3+ TReg cell population isolated from the secondary lymphoid organs of wild-type mice contained two subsets: a NRP1hi subset (70–80% of total FOXP3+ T cells) and a NRP1low subset (20–30% of total FOXP3+ T cells). Notably, high NRP1 levels on TReg cells correlated with expression of Helios (a transcription factor previously implicated as a marker of natural TReg cells), whereas Weiss et al. showed that low NRP1 levels correlated with the expression of death-associated protein-like 1 (DAPL1), which is absent from natural TReg cells.

Interestingly, most FOXP3+ TReg cells derived from naive CD4+ T cells that had been transferred into congenic recipients were found by both groups to be NRP1low. Moreover, NRP1lowFOXP3+ T cells were almost undetectable in the thymus, but were enriched in colonic lamina propria, which is a major site of peripheral TReg cell induction. In keeping with reports that the intestinal microbiota drives TReg cell induction, Weiss et al. detected lower numbers of gut-associated NRP1low TReg cells in germ-free mice than in specific pathogen-free mice. Based on these and other data, the two groups recommend the use of NRP1 as a surface marker to distinguish natural TReg cells from induced TReg cells in the steady state.

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References

ORIGINAL RESEARCH PAPERS

  1. Yadav, M. et al. Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. J. Exp. Med. 10 Sep 2012 (doi:10.1084/jem.20120822)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Weiss, J. M. et al. Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells. J. Exp. Med. 10 Sep 2012 (doi:10.1084/jem.20120914)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

FURTHER READING

  1. Hsieh, C. S. et al. Selection of regulatory T cells in the thymus. Nature Rev. Immunol. 12, 157–167 (2012)

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Authors
  1. Maria Papatriantafyllou
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Papatriantafyllou, M. Neuropilin 1 — distinguishing TReg cell subsets. Nat Rev Immunol 12, 746–747 (2012). https://doi.org/10.1038/nri3323

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