title: Alterations of the immunosuppressive IL4I1 enzyme activity induced by naturally occurring SNP/mutations.
abstract: The immunosuppressive phenylalanine oxidase interleukin 4-induced gene 1 (IL4I1), primarily produced by antigen-presenting cells, inhibits T-cell proliferation and promotes the generation of Foxp3(+) regulatory T cells in vitro. Highly expressed by tumour-associated macrophages from human cancers, IL4I1 has a potential role in immune evasion from the anti-tumour immune response. We have reviewed single-nucleotide polymorphisms (SNPs) and mutations described for the exon 4 of the IL4I1 isoform 1, which is expressed in lymphoid tissue. Two of them were expressed in an exogenous system to analyse their effect on the enzymatic activity. The N92D SNP leads to a hyperactive enzyme, while the R102G mutation is hypomorphic. Moreover, we show that IL4I1 activity is not only directed against phenylalanine, as initially described, but also at a lower level against arginine. These data pave the way to more extensive analyses of the mutational state of IL4I1 in pathological conditions such as cancer, where its participation in immune system dysfunctions may have therapeutic implications.
authors.affiliation: INSERM U955, Equipe 09 and Equipe 00, Créteil, France.|Université Paris Est, Faculté de Médecine, Créteil, France.|AP-HP, Hôpital H. Mondor-A. Chenevier, Service d'Immunologie Biologique, Créteil, France.
authors.forename: V
authors.initials: V
authors.lastname: Molinier-Frenkel
authors.affiliation: INSERM U955, Equipe 09 and Equipe 00, Créteil, France.|Université Paris Est, Faculté de Médecine, Créteil, France.
authors.forename: D
authors.initials: D
authors.lastname: Mestivier
authors.affiliation: INSERM U955, Equipe 09 and Equipe 00, Créteil, France.|Université Paris Est, Faculté de Médecine, Créteil, France.|AP-HP, Hôpital H. Mondor-A. Chenevier, Service d'Immunologie Biologique, Créteil, France.
authors.forename: F
authors.initials: F
authors.lastname: Castellano
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D005091:Exons; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007438:Introns; D050830:L-Amino Acid Oxidase / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D008995:Monoamine Oxidase / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D040681:Structural Homology, Protein; D019139:Tumor Escape / Q000235:genetics*; D017819:Viperidae / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D010649:Phenylalanine; D001120:Arginine; C105158:IL4I1 protein, human; D050830:L-Amino Acid Oxidase; D008995:Monoamine Oxidase