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Inducible Costimulator (ICOS) facilitates T-dependent B cell differentiation by augmenting IL-4 translation

Mathieu Gigoux1, 2*, Amanda Lovato1, 2, Julien Leconte1, 3, Joanne Leung1, 2, Nahum Sonenberg4, 5 and Woong-Kyung Suh1, 2, 3
  • 1 Institut de Recherches Cliniques de Montréal, Canada
  • 2 McGill University, Microbiology and Immunology, Canada
  • 3 Université de Montréal, Médecine, Canada
  • 4 McGill University, Biochemistry, Canada
  • 5 The Rosalind and Morris Goodman Cancer Research Centre, Canada

The Inducible Costimulator (ICOS) is a member of the CD28 family of costimulatory receptor that is highly expressed in follicular helper T cells (Tfh), a subset of CD4 T cells that migrate to the B cell zone and facilitate germinal center reactions. Although ICOS is known to play a critical role in shaping the Tfh cell population during immune reactions, its role in the effector function of Tfh cells has been unclear. Here we demonstrate that ICOS assists TCR-mediated signal transduction by potentiating PI3K-Akt-mTOR signaling cascade that leads to hyperphosphorylation of the key translational regulators p70S6K and 4E-BP1. Consistently, ICOS costimulation promotes the formation of polysomes on IL-4 mRNA in a PI3K-signaling dependent manner. Here we provide evidence that IL-4 production is diminished during T-B cell co-culture when ICOS-PI3K signaling axis is disrupted in T cells. We also show that the 5’ untranslated region of IL-4 mRNA is able to repress the translation of firefly luciferase. Thus, ICOS-PI3K signaling facilitates translation of IL-4 mRNA and this may augment IL-4 production during T-B interaction in germinal centers.

Keywords: ICOS, IL-4, PI3K/AKT/mTOR, translation, costimulation

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Immune receptors and signaling

Citation: Gigoux M, Lovato A, Leconte J, Leung J, Sonenberg N and Suh W (2013). Inducible Costimulator (ICOS) facilitates T-dependent B cell differentiation by augmenting IL-4 translation. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00538

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Received: 10 Jun 2013; Published Online: 22 Aug 2013.

* Correspondence: Mr. Mathieu Gigoux, Institut de Recherches Cliniques de Montréal, Montréal, Canada, Mathieu.Gigoux@ircm.qc.ca