Differential expression of the immunosuppressive enzyme IL4I1 in human induced Aiolos+, but not natural Helios+, FOXP3+ Treg cells

Clara-Maria Scarlata; Clotilde Celse; Pascale Pignon; Maha Ayyoub; Danila Valmori

doi:10.1002/eji.201444897

Differential expression of the immunosuppressive enzyme IL4I1 in human induced Aiolos+, but not natural Helios+, FOXP3+ Treg cells

Eur J Immunol. 2015 Feb;45(2):474-9. doi: 10.1002/eji.201444897. Epub 2015 Jan 16.

Authors

Clara-Maria Scarlata¹, Clotilde Celse, Pascale Pignon, Maha Ayyoub, Danila Valmori

Affiliation

¹ Institut National de la Santé et de la Recherche Médicale, Unité 1102, Equipe Labellisée Ligue Contre le Cancer, Institut de Cancérologie de l'Ouest, Nantes-Saint Herblain, France.

PMID: 25446972
DOI: 10.1002/eji.201444897

Abstract

IL4I1 encodes an L-phenylalanine oxidase that inhibits T-cell proliferation. It has been recently reported that IL4I1 is expressed in TH17 cells as part of a mechanism that limits their pathogenicity. We have previously identified a population of human FOXP3(+) Treg cells that secrete IL-17 ex vivo; here, we addressed the expression of IL4I1 in that Treg-cell population. We found that in ex vivo isolated circulating Treg cells, IL4I1 expression is induced by activation. Moreover, IL4I1 expression is restricted to cells that do not express Helios, a transcription factor that characterizes natural Treg cells, but that express Aiolos, which is involved in the differentiation of TH17 and induced Treg cells. We also showed that conversion of Treg cells under inflammatory conditions increases IL4I1 expression, likely as part of a regulatory loop that attempts to limit the pathogenicity resulting from their conversion into TH17. The specific expression of IL4I1 in TH17 and iTreg cells may provide insights into approaches that aim at modulating these populations in different pathological conditions involving inflammation-mediated immunosuppression.

Keywords: FOXP3+ Treg; IL4I1; Immune regulation; Immunosuppressive enzymes; TH17.

Publication types

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

MeSH terms

Cell Communication
Cell Differentiation
Forkhead Transcription Factors / genetics*
Forkhead Transcription Factors / immunology
Gene Expression Regulation / immunology
Humans
Ikaros Transcription Factor / genetics*
Ikaros Transcription Factor / immunology
Immune Tolerance
Interleukin-17 / genetics
Interleukin-17 / immunology
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / immunology
Ionomycin / pharmacology
L-Amino Acid Oxidase / genetics*
L-Amino Acid Oxidase / immunology
Lymphocyte Activation
Signal Transduction
T-Lymphocytes, Regulatory / cytology
T-Lymphocytes, Regulatory / drug effects
T-Lymphocytes, Regulatory / immunology
T-Lymphocytes, Regulatory / metabolism*
Tetradecanoylphorbol Acetate / pharmacology
Th17 Cells / cytology
Th17 Cells / drug effects
Th17 Cells / immunology
Th17 Cells / metabolism*
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / immunology

Substances

FOXP3 protein, human
Forkhead Transcription Factors
IKZF2 protein, human
IKZF3 protein, human
Interleukin-17
Intracellular Signaling Peptides and Proteins
TOB1 protein, human
Tumor Suppressor Proteins
Ikaros Transcription Factor
Ionomycin
IL4I1 protein, human
L-Amino Acid Oxidase
Tetradecanoylphorbol Acetate