The costimulatory molecule CD226 signals through VAV1 to amplify TCR signals and promote IL-17 production by CD4(+) T cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Science Signaling Année : 2018

The costimulatory molecule CD226 signals through VAV1 to amplify TCR signals and promote IL-17 production by CD4(+) T cells

Résumé

The activation of T cells requires the guanine nucleotide exchange factor VAV1. Using mice in which a tag for affinity purification was attached to endogenous VAV1 molecules, we analyzed by quantitative mass spectrometry the signaling complex that assembles around activated VAV1. Fifty VAV1-binding partners were identified, most of which had not been previously reported to participate in VAV1 signaling. Among these was CD226, a costimulatory molecule of immune cells. Engagement of CD226 induced the tyrosine phosphorylation of VAV1 and synergized with T cell receptor (TCR) signals to specifically enhance the production of interleukin-17 (IL-17) by primary human CD4(+) T cells. Moreover, co-engagement of the TCR and a risk variant of CD226 that is associated with autoimmunity (rs763361) further enhanced VAV1 activation and IL-17 production. Thus, our study reveals that a VAV1-based, synergistic cross-talk exists between the TCR and CD226 during both physiological and pathological T cell responses and provides a rational basis for targeting CD226 for the management of autoimmune diseases.

Domaines

Immunologie

Dates et versions

hal-02117993 , version 1 (02-05-2019)

Identifiants

Citer

Guillaume Gaud, Romain Roncagalli, Karima Chaoui, Isabelle Bernard-Cadenat, Julien Familiades, et al.. The costimulatory molecule CD226 signals through VAV1 to amplify TCR signals and promote IL-17 production by CD4(+) T cells. Science Signaling, 2018, 11 (538), ⟨10.1126/scisignal.aar3083⟩. ⟨hal-02117993⟩
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