The Shc family protein adaptor, Rai, acts as a negative regulator of Th17 and Th1 cell development

Maria Teresa Savino, Cristina Ulivieri, Giacomo Emmi, Domenico Prisco, Giulia de Falco, Barbara Ortensi, Enrico Beccastrini, Lorenzo Emmi, Giuliana Pelicci, Mario M. D'Elios, Cosima T. Baldari

Research output: Contribution to journalArticle

Abstract

Rai, a Shc adapter family member, acts as a negative regulator of antigen receptor signaling in T and B cells. Rai-/- mice develop lupus-like autoimmunity associated to the spontaneous activation of self-reactive lymphocytes. Here, we have addressed the potential role of Rai in the development of the proinflammatory Th1 and Th17 subsets, which are centrally implicated in the pathogenesis of a number of autoimmune diseases, including lupus. We show that Rai-/- mice display a spontaneous Th1/Th17 bias. In vitro polarization experiments on naive and effector/memory CD4++ T cells demonstrate that Rai-/- favors the development and expansion of Th17 but not Th1 cells, indicating that Rai modulates TCR signaling to antagonize the pathways driving naive CD4++ T cell differentiation to the Th17 lineage, while indirectly limiting Th1 cell development in vivo. Th1 and Th17 cell infiltrates were found in the kidneys of Rai-/- mice, providing evidence that Rai-/- contributes to the development of lupus nephritis, not only by enhancing lymphocyte activation but also by promoting the development and expansion of proinflammatory effector T cells. Interestingly, T cells from SLE patients were found to have a defect in Rai expression, suggesting a role for Rai in disease pathogenesis.

Original languageEnglish
Pages (from-to)549-559
Number of pages11
JournalJournal of Leukocyte Biology
Volume93
Issue number4
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Cell differentiation
  • Signal transduction
  • Systemic lupus erythematosus
  • T cell receptors
  • Th2 cells

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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  • Cite this

    Savino, M. T., Ulivieri, C., Emmi, G., Prisco, D., de Falco, G., Ortensi, B., Beccastrini, E., Emmi, L., Pelicci, G., D'Elios, M. M., & Baldari, C. T. (2013). The Shc family protein adaptor, Rai, acts as a negative regulator of Th17 and Th1 cell development. Journal of Leukocyte Biology, 93(4), 549-559. https://doi.org/10.1189/jlb.0712331