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Article dans une revue

OX40L/OX40 axis impairs follicular and natural Treg function in human SLE

Clément Jacquemin 1 Jean-François Augusto 2 Marc Scherlinger 3 Noémie Gensous Edouard Forcade 4 Isabelle Douchet 4 Emeline Levionnois 5 Christophe Richez 6 Estibaliz Lazaro 7 Pierre Duffau 8 Marie-Elise Truchetet 9 Julien Seneschal 1 Lionel Couzi 10 Jean-Luc Pellegrin 11 Jean-François Viallard 8 Thierry Schaeverbeke 12 Virginia Pascual 13 Cécile Contin-Bordes 4 Patrick Blanco 14
1 Biothérapies des maladies génétiques et cancers
2 CRCINA-ÉQUIPE 7 - Innate Immunity and Immunotherapy
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
3 UB - Université de Bordeaux
4 CIRID - Composantes innées de la réponse immunitaire et différenciation
5 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
6 Hôpital Pellegrin
7 Hôpital Haut-Lévêque [CHU Bordeaux]
8 Service de médecine interne et maladies infectieuses [Bordeaux]
9 Immunology and Allergy
10 Service de Néphrologie-transplantation-dialyse [Bordeaux]
11 CH F. Quesnay - Service de médecine interne
12 Service de rhumatologie
13 BIIR - Baylor Institute for Immunology Research
14 ImmunoConcept - Immunology from Concept and Experiments to Translation
Abstract :

Tregs are impaired in human systemic lupus erythematosus (SLE) and contribute to effector T cell activation. However, the mechanisms responsible for the Treg deficiency in SLE remain unclear. We hypothesized that the OX40L/OX40 axis is implicated in Treg and regulatory follicular helper T (Tfr) cell dysfunction in human SLE. OX40L/OX40 axis engagement on Tregs and Tfr cells not only specifically impaired their ability to regulate effector T cell proliferation, but also their ability to suppress T follicular helper (Tfh) cell-dependent B cell activation and immunoglobulin secretion. Antigen-presenting cells from patients with active SLE mediated Treg dysfunction in an OX40L-dependent manner, and OX40L-expressing cells colocalized with Foxp3+ cells in active SLE skin lesions. Engagement of the OX40L/OX40 axis resulted in Foxp3 downregulation in Tregs, and expression in SLE Tregs correlated with the proportion of circulating OX40L-expressing myeloid DCs. These data support that OX40L/OX40 signals are implicated in Treg dysfunction in human SLE. Thus, blocking the OX40L/OX40 axis appears to be a promising therapeutic strategy.

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https://hal.univ-angers.fr/hal-02874595
Contributeur : Okina Université d'Angers <>
Soumis le : vendredi 19 juin 2020 - 02:50:52
Dernière modification le : mercredi 19 août 2020 - 11:18:02

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UNIV-ANGERS | CRCINA-3I | CRCINA | UNIV-NANTES | CNRS | UNIV-PARIS5 | UP-SANTE | USPC | UNIV-PARIS

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Clément Jacquemin, Jean-François Augusto, Marc Scherlinger, Noémie Gensous, Edouard Forcade, et al.. OX40L/OX40 axis impairs follicular and natural Treg function in human SLE. JCI Insight, American Society for Clinical Investigation, 2018, 3 (24), pp.e122167. ⟨10.1172/jci.insight.122167⟩. ⟨hal-02874595⟩

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