title: Differential expression of the immunosuppressive enzyme IL4I1 in human induced Aiolos+, but not natural Helios+, FOXP3+ Treg cells.
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.
authors.affiliation: 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.
authors.forename: Clara-Maria
authors.initials: CM
authors.lastname: Scarlata
authors.forename: Clotilde
authors.initials: C
authors.lastname: Celse
authors.forename: Pascale
authors.initials: P
authors.lastname: Pignon
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
mesh_terms: D002450:Cell Communication; D002454:Cell Differentiation; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics* / Q000276:immunology; D007108:Immune Tolerance; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D015759:Ionomycin / Q000494:pharmacology; D050830:L-Amino Acid Oxidase / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C111431:IKZF2 protein, human; C106285:IKZF3 protein, human; D020381:Interleukin-17; D047908:Intracellular Signaling Peptides and Proteins; C098669:TOB1 protein, human; D025521:Tumor Suppressor Proteins; D051740:Ikaros Transcription Factor; D015759:Ionomycin; C105158:IL4I1 protein, human; D050830:L-Amino Acid Oxidase; D013755:Tetradecanoylphorbol Acetate
keywords: FOXP3+ Treg; IL4I1; Immune regulation; Immunosuppressive enzymes; TH17