Differential expression of the immunosuppressive enzyme IL4I1 in human induced Aiolos super(+), but not natural Helios super(+), FOXP3 super(+) 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
• 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 T sub(H)17 cells as part of a mechanism that limits their pathogenicity. We have previously identified a population of human FOXP3 super(+) 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 T sub(H)17 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 T sub(H)17. The specific expression of IL4I1 in T sub(H)17 and iTreg cells may provide insights into approaches that aim at modulating these populations in different pathological conditions involving inflammation-mediated immunosuppression.