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Blood, 1 July 2007, Vol. 110, No. 1, pp. 220-227. Prepublished online as a Blood First Edition Paper on March 13, 2007; DOI 10.1182/blood-2006-07-036210. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-036210v1 110/1/220    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Boulland, M.-L. Articles by Castellano, F. Search for Related Content PubMed PubMed Citation Articles by Boulland, M.-L. Articles by Castellano, F. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Human IL4I1 is a secreted L-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation Marie-Laure Boulland1,2, Jeanine Marquet1,2, Valérie Molinier-Frenkel1,2,3, Peter Möller4, Chrystelle Guiter1,2, Fanette Lasoudris1, Christiane Copie-Bergman1,2,5, Maryse Baia1,5, Philippe Gaulard1,1,2,5, Karen Leroy1,2,5, and Flavia Castellano1,2,3 1 Institut National de la Santé et de la Recherche Medicale (INSERM), Unité 841, Institut Mondor de Recherche Médicale (IMRB), Département Immunologie-Oncologie-Dermatologie, Equipe 09, Créteil, France; 2 Université Paris12, Faculté de Médecine, Institut Federatif de Recherche (IFR)10, Créteil, France; 3 Assistance Publique-Hopitaux de Paris (AP-HP), Groupe Henri Mondor-Albert Chenevier, Service d'Immunologie Biologique, Créteil, France; 4 Abteilung für Pathologie des Universitätklinikums Ulm, Germany; 5 AP-HP, Groupe Henri Mondor-Albert Chenevier, Service de Pathologie, Créteil, France Interleukin-4–induced gene 1 (IL4I1) was first described as a B-cell IL4-inducible gene and is highly expressed in primary mediastinal B-cell lymphomas. We established stable HEK293 clones expressing human and mouse IL4I1 to examine their biochemical properties and function. Both proteins were secreted into the culture medium, and we observed the secretion of endogenous human IL4I1 (hIL4I1) protein in a mediastinal lymphoma B-cell line, MedB-1. We showed that IL4I1 has L-amino acid oxidase activity, optimal at physiological pH and primarily directed toward phenylalanine. Immunohistochemical analysis of secondary lymphoid organs showed staining of germinal center macrophages and inflammatory myeloid cells. In vitro, functional enzyme was highest in mature dendritic cells (DCs), suggesting a role in antigen-presenting cell/T-lymphocyte cross-talk. Indeed, hIL4I1 inhibited the proliferation of CD3-stimulated T lymphocytes with a similar effect on CD4+ and CD8+ T cells. In contrast, memory T cells were more strongly affected by hIL4I1 and its catabolite H2O2 than naive T cells. hIL4I1 inhibitory effect was dependent on enzymatic activity and H2O2 production and associated with a transient down-regulation of TCR expression. Altogether these data suggest IL4I1 as a new immunomodulatory enzyme produced by DCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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