Expression of Helios, an Ikaros Transcription Factor Family Member, Differentiates Thymic-Derived from Peripherally Induced Foxp3+ T Regulatory Cells

By A. Thornton, P. Korty, D. Tran, E. Wohlfert, Patrick E Murray, Y. Belkaid, E. Shevach. Journal of Immunology, 2010

1,432 citations recorded by the source corpus.

Helios, a member of the Ikaros transcription factor family, is preferentially expressed at the mRNA level by regulatory T cells (Treg cells). We evaluated Helios protein expression using a newly generated mAb and demonstrated that it is expressed in all thymocytes at the double negative 2 stage of thymic development. Although Helios was expressed by 100% of CD4+CD8−Foxp3+ thymocytes, its expression in peripheral lymphoid tissues was restricted to a subpopulation (∼70%) of Foxp3+ T cells in mice and humans. Neither mouse nor human naive T cells induced to express Foxp3 in vitro by TCR stimulation in the presence of TGF-β expressed Helios. Ag-specific Foxp3+ T cells induced in vivo by Ag feeding also failed to express Helios. Collectively, these results demonstrate that Helios is potentially a specific marker of thymic-derived Treg cells and raises the possibility that a significant percentage of Foxp3+ Treg cells are generated extrathymically.

Subfields: Immunology, Pediatrics, Perinatology and Child Health, Surgery

View Paper: https://www.semanticscholar.org/paper/8593c4a8d0454d232afdd934a2289773c132ecec

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Surgery

J. Bluestone

Citations in the corpus

Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. (2011, background): “1+FoxP3+ Treg cells in the mLN homogenously expressed the Treg cell marker GITR (data not shown) and lacked expression of the transcription factor helios (Figure 2B), which has been suggested to discriminate between helios+ natural Treg cells and helios! induced Treg cells (Thornton et al., 2010).”
Peripheral CD4 T cell differentiation regulated by networks of cytokines and transcription factors (2010, background): “Another Ikaros family protein, Helios, is expressed in nTregs but not in iTregs (105); however, the function of Helios in nTregs has not been determined.”
Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. (2012, background): “BothCD25 or lo andCD25 RFP or Foxp3 cells showed lower Helios expression than did RFPFoxp3 cells, a finding supporting the idea that peripherally induced Treg (iTreg) cells are Helios (Figure 6C; Thornton et al., 2010).”
Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo (2012, background): “Nearly 70% of Foxp3+ T reg cells expressed Nrp-1 in WT NOD or B6 mice correlating with Helios expression (Fig. 2 c; Thornton et al., 2010), suggesting that Nrp-1hi T reg cells were thymically derived, whereas Nrp-1lo T reg cells represented a Figure 1.”
The microbial metabolites, short chain fatty acids, regulate colonic Treg cell homeostasis (2013, background): “These populations can be distinguished by expression of Helios, which in vivo is restricted to nTregs (11).”
The Microbiome in Infectious Disease and Inflammation (2012, neutral): “A lower level of Helios expression has been proposed to be characteristic of iTreg cells (225).”