IL-4–Induced Gene 1: A Negative Immune Checkpoint Controlling B Cell Differentiation and Activation
| Autor: | Armelle Prévost-Blondel, Elena Rondeau, Renée Lengagne, Fériel Bekkat, Yolande Richard, Valérie Molinier-Frenkel, Laetitia Douguet, Flavia Castellano, Cédric Auffray, Lloyd Bod |
|---|---|
| Přispěvatelé: | Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Immunologie et Oncogenese des Tumeurs Lymphoides, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Equipe 09, Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Immunology Immunoglobulins Receptors Antigen B-Cell L-Amino Acid Oxidase Lymphocyte Activation 03 medical and health sciences Mice Immune system Antigen Plasma cell differentiation medicine Immunology and Allergy Animals Syk Kinase Interleukin 4 B cell ComputingMilieux_MISCELLANEOUS Mice Knockout B-Lymphocytes Flavoproteins Chemistry Protein Tyrosine Phosphatase Non-Receptor Type 6 Ribosomal Protein S6 Kinases Germinal center Cell Differentiation Immune checkpoint Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology [SDV.IMM]Life Sciences [q-bio]/Immunology Amino Acid Oxidoreductases Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2018, 200 (3), pp.1027-1038. ⟨10.4049/jimmunol.1601609⟩ Journal of Immunology, 2018, 200 (3), pp.1027-1038. ⟨10.4049/jimmunol.1601609⟩ |
| ISSN: | 0022-1767 1550-6606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|