IL-4-Induced Gene 1: A Negative Immune Checkpoint Controlling B Cell Differentiation and Activation.

Autor:	Bod L; INSERM, U1016, Institut Cochin, 75014 Paris, France.; CNRS, UMR8104, 75014 Paris, France.; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France., Douguet L; INSERM, U1016, Institut Cochin, 75014 Paris, France.; CNRS, UMR8104, 75014 Paris, France.; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France., Auffray C; INSERM, U1016, Institut Cochin, 75014 Paris, France.; CNRS, UMR8104, 75014 Paris, France.; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France., Lengagne R; INSERM, U1016, Institut Cochin, 75014 Paris, France.; CNRS, UMR8104, 75014 Paris, France.; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France., Bekkat F; INSERM, U1016, Institut Cochin, 75014 Paris, France.; CNRS, UMR8104, 75014 Paris, France.; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France., Rondeau E; INSERM, U1016, Institut Cochin, 75014 Paris, France.; CNRS, UMR8104, 75014 Paris, France.; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France., Molinier-Frenkel V; INSERM, U955, Equipe 09, 94000 Créteil, France.; Faculté de Médecine, Université Paris Est, 94000 Créteil, France.; Assistance Publique - Hôpitaux de Paris, Hôpital Henri Mondor - Albert Chenevier, Service d'Immunologie Biologique, 94000 Créteil, France; and., Castellano F; INSERM, U955, Equipe 09, 94000 Créteil, France.; Faculté de Médecine, Université Paris Est, 94000 Créteil, France.; Assistance Publique - Hôpitaux de Paris, Hôpital Henri Mondor - Albert Chenevier, Plateforme de Ressources Biologiques, 94000 Créteil, France., Richard Y; INSERM, U1016, Institut Cochin, 75014 Paris, France; armelle.blondel@inserm.fr yolande.richard@inserm.fr.; CNRS, UMR8104, 75014 Paris, France.; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France., Prévost-Blondel A; INSERM, U1016, Institut Cochin, 75014 Paris, France; armelle.blondel@inserm.fr yolande.richard@inserm.fr.; CNRS, UMR8104, 75014 Paris, France.; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Feb 01; Vol. 200 (3), pp. 1027-1038. Date of Electronic Publication: 2017 Dec 29.
DOI:	10.4049/jimmunol.1601609
Abstrakt:	Emerging data highlight the crucial role of enzymes involved in amino acid metabolism in immune cell biology. IL-4-induced gene-1 (IL4I1), a secreted l-phenylalanine oxidase expressed by APCs, has been detected in B cells, yet its immunoregulatory role has only been explored on T cells. In this study, we show that IL4I1 regulates multiple steps in B cell physiology. Indeed, IL4I1 knockout mice exhibit an accelerated B cell egress from the bone marrow, resulting in the accumulation of peripheral follicular B cells. They also present a higher serum level of natural Igs and self-reactive Abs. We also demonstrate that IL4I1 produced by B cells themselves controls the germinal center reaction, plasma cell differentiation, and specific Ab production in response to T dependent Ags, SRBC, and NP-KLH. In vitro, IL4I1-deficient B cells proliferate more efficiently than their wild-type counterparts in response to BCR cross-linking. Moreover, the absence of IL4I1 increases activation of the Syk-Akt-S6kinase signaling pathway and calcium mobilization, and inhibits SHP-1 activity upon BCR engagement, thus supporting that IL4I1 negatively controls BCR-dependent activation. Overall, our study reveals a new perspective on IL4I1 as a key regulator of B cell biology. (Copyright © 2018 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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