Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease

Masaki Miyazaki; Kazuko Miyazaki; Shuwen Chen; Manami Itoi; Marina Miller; Li-Fan Lu; Nissi Varki; Aaron N Chang; David H Broide; Cornelis Murre

doi:10.1038/ni.2928

Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease

Nat Immunol. 2014 Aug;15(8):767-76. doi: 10.1038/ni.2928. Epub 2014 Jun 29.

Authors

Affiliations

¹ 1] Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA. [2].
² Department of Immunology and Microbiology, Meiji University of Integrative Medicine, Hiyoshi-cho, Kyoto, Japan.
³ Department of Medicine, University of California, San Diego, La Jolla, California, USA.
⁴ Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA.
⁵ Department of Pathology, University of California, San Diego, La Jolla, California, USA.
⁶ Center for Computational Biology, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California, USA.

PMID: 24973820
PMCID: PMC4365819
DOI: 10.1038/ni.2928

Abstract

Regulatory T (Treg) cells suppress the development of inflammatory disease, but our knowledge of transcriptional regulators that control this function remains incomplete. Here we show that expression of Id2 and Id3 in Treg cells was required to suppress development of fatal inflammatory disease. We found that T cell antigen receptor (TCR)-driven signaling initially decreased the abundance of Id3, which led to the activation of a follicular regulatory T (TFR) cell-specific transcription signature. However, sustained lower abundance of Id2 and Id3 interfered with proper development of TFR cells. Depletion of Id2 and Id3 expression in Treg cells resulted in compromised maintenance and localization of the Treg cell population. Thus, Id2 and Id3 enforce TFR cell checkpoints and control the maintenance and homing of Treg cells.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Base Sequence
CD8-Positive T-Lymphocytes / immunology
Cell Differentiation / immunology
Cell Movement / immunology
Cell Proliferation
Female
Forkhead Transcription Factors / biosynthesis
Gene Expression Regulation / immunology
Green Fluorescent Proteins / genetics
Inflammation / genetics
Inflammation / immunology*
Inhibitor of Differentiation Protein 2 / biosynthesis
Inhibitor of Differentiation Protein 2 / genetics
Inhibitor of Differentiation Protein 2 / immunology*
Inhibitor of Differentiation Proteins / biosynthesis
Inhibitor of Differentiation Proteins / genetics
Inhibitor of Differentiation Proteins / immunology*
Interleukin-10 / biosynthesis
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Antigen, T-Cell / immunology
Receptors, CXCR5 / biosynthesis
Sequence Analysis, RNA
T-Lymphocytes, Regulatory / immunology*

Substances

CXCR5 protein, mouse
Forkhead Transcription Factors
Foxp3 protein, mouse
IL10 protein, mouse
Idb2 protein, mouse
Inhibitor of Differentiation Protein 2
Inhibitor of Differentiation Proteins
Receptors, Antigen, T-Cell
Receptors, CXCR5
Interleukin-10
Idb3 protein, mouse
Green Fluorescent Proteins

Associated data

GEO/GSE57682

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding