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

• Published in: European journal of immunology 2015-02, Vol.45 (2), p.474-479
• Main Authors: Scarlata, Clara‐Maria, Celse, Clotilde, Pignon, Pascale, Ayyoub, Maha, Valmori, Danila
• Format: Article
• Language: English
• Subjects: Cell Communication; Cell Differentiation; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - immunology; FOXP3+ Treg; Gene Expression Regulation - immunology; Humans; Ikaros Transcription Factor - genetics; Ikaros Transcription Factor - immunology; IL4I1; Immune regulation; Immune Tolerance; Immunosuppressive enzymes; 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 cell receptors; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Tetradecanoylphorbol Acetate - pharmacology; TH17; Th17 Cells - cytology; Th17 Cells - drug effects; Th17 Cells - immunology; Th17 Cells - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201444897

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.