Generation of Helios reporter mice and an evaluation of the suppressive capacity of Helios(+) regulatory T cells in vitro

Kazunari Sugita; Sho Hanakawa; Tetsuya Honda; Gen Kondoh; Yoshiki Miyachi; Kenji Kabashima; Takashi Nomura

doi:10.1111/exd.12711

Generation of Helios reporter mice and an evaluation of the suppressive capacity of Helios(+) regulatory T cells in vitro

Exp Dermatol. 2015 Jul;24(7):554-6. doi: 10.1111/exd.12711. Epub 2015 May 4.

Authors

Kazunari Sugita^{1

2}, Sho Hanakawa¹, Tetsuya Honda¹, Gen Kondoh³, Yoshiki Miyachi¹, Kenji Kabashima¹, Takashi Nomura¹

Affiliations

¹ Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
² Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan.
³ Laboratory of Animal Experiments for Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.

PMID: 25846704
DOI: 10.1111/exd.12711

Abstract

Helios is a member of the Ikaros transcription factor family and has been reported to be a marker of thymus-derived regulatory T cells (Treg). Helios is an intracellular protein, however, and hence cannot be used as a marker to separate living Tregs. To solve this problem, we generated Helios reporter mice in which Helios+ cells selectively express Venus, a variant of green fluorescent protein. Most of the Tregs in the thymus expressed Helios, whereas its expression was varied in peripheral lymphoid organs. The Helios+ Treg-population was superior in ability to suppress both antigen-specific and TCR-stimulated T cell responses. We also showed that Helios+ Tregs inhibited the cytokine production by T cells more efficiently than Helios- Tregs. We conclude that Helios reporter mouse strain is a useful tool to study function of Helios and that Helios+ Tregs represent the highly suppressive population.

Keywords: Foxp3; Helios; Treg; contact hypersensitivity; lymph node.

Publication types

Letter
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / immunology*
DNA-Binding Proteins / metabolism
Dermatitis, Contact / genetics
Dermatitis, Contact / immunology
Dermatitis, Contact / metabolism
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / metabolism
Gene Expression
Genes, Reporter
Immune Tolerance / genetics
In Vitro Techniques
Interferon-gamma / biosynthesis
Interleukin-17 / biosynthesis
Luminescent Proteins / genetics
Luminescent Proteins / metabolism
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Transgenic
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
T-Lymphocytes, Regulatory / classification
T-Lymphocytes, Regulatory / immunology*
T-Lymphocytes, Regulatory / metabolism
Transcription Factors / genetics*
Transcription Factors / immunology*
Transcription Factors / metabolism
Transforming Growth Factor beta / biosynthesis

Substances

Bacterial Proteins
DNA-Binding Proteins
Forkhead Transcription Factors
Foxp3 protein, mouse
Interleukin-17
Luminescent Proteins
Recombinant Fusion Proteins
Transcription Factors
Transforming Growth Factor beta
Zfpn1a2 protein, mouse
yellow fluorescent protein, Bacteria
Interferon-gamma