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An Overview of l-Amino Acid Oxidase Functions from Bacteria to Mammals: Focus on the Immunoregulatory Phenylalanine Oxidase IL4I1

The Mondor Institute of Biomedical Research (IMRB), INSERM U955, Team 09, F-94010 Créteil CEDEX, France
Faculty of Medicine, Paris Est University, F-94010 Créteil CEDEX, France
Biological Resources Platform, Henri Mondor Hospital, AP-HP, F-94010 Créteil, France
Department of Hematology-Immunology, Henri Mondor Hospital, AP-HP, F-94010 Créteil, France
Authors to whom correspondence should be addressed.
Molecules 2017, 22(12), 2151;
Received: 7 November 2017 / Revised: 23 November 2017 / Accepted: 29 November 2017 / Published: 5 December 2017
(This article belongs to the Special Issue Flavoenzymes)
l-amino acid oxidases are flavin adenine dinucleotide-dependent enzymes present in all major kingdom of life, from bacteria to mammals. They participate in defense mechanisms by limiting the growth of most bacteria and parasites. A few mammalian LAAOs have been described, of which the enzyme “interleukin-4 induced gene 1” (IL4I1) is the best characterized. IL4I1 mainly oxidizes l-phenylalanine. It is a secreted enzyme physiologically produced by antigen presenting cells of the myeloid and B cell lineages and T helper type (Th) 17 cells. Important roles of IL4I1 in the fine control of the adaptive immune response in mice and humans have emerged during the last few years. Indeed, IL4I1 inhibits T cell proliferation and cytokine production and facilitates naïve CD4+ T-cell differentiation into regulatory T cells in vitro by limiting the capacity of T lymphocytes to respond to clonal receptor stimulation. It may also play a role in controlling the germinal center reaction for antibody production and limiting Th1 and Th17 responses. IL4I1 is expressed in tumor-associated macrophages of most human cancers and in some tumor cell types. Such expression, associated with its capacity to facilitate tumor growth by inhibiting the anti-tumor T-cell response, makes IL4I1 a new potential druggable target in the field of immunomodulation in cancer. View Full-Text
Keywords: IL4I1; immunosuppression; l-amino acid oxidase IL4I1; immunosuppression; l-amino acid oxidase
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Castellano, F.; Molinier-Frenkel, V. An Overview of l-Amino Acid Oxidase Functions from Bacteria to Mammals: Focus on the Immunoregulatory Phenylalanine Oxidase IL4I1. Molecules 2017, 22, 2151.

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