Wnt/β-Catenin Signaling Induces Integrin α4β1 in T Cells and Promotes a Progressive Neuroinflammatory Disease in Mice

Daniele Sorcini, Stefano Bruscoli, Tiziana Frammartino, Monica Cimino, Emanuela Mazzon, Maria Galuppo, Placido Bramanti, Mumna Al-Banchaabouchi, Dominika Farley, Olga Ermakova, Olga Britanova, Mark Izraelson, Dmitry Chudakov, Michele Biagioli, Paolo Sportoletti, Sara Flamini, Marcello Raspa, Ferdinando Scavizzi, Claus Nerlov, Graziella MiglioratiCarlo Riccardi, Oxana Bereshchenko

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanisms leading to autoimmune and inflammatory diseases in the CNS have not been elucidated. The environmental triggers of the aberrant presence of CD4+ T cells in the CNS are not known. In this article, we report that abnormal β-catenin expression in T cells drives a fatal neuroinflammatory disease in mice that is characterized by CNS infiltration of T cells, glial activation, and progressive loss of motor function. We show that enhanced β-catenin expression in T cells leads to aberrant and Th1-biased T cell activation, enhanced expression of integrin α4β1, and infiltration of activated T cells into the spinal cord, without affecting regulatory T cell function. Importantly, expression of β-catenin in mature naive T cells was sufficient to drive integrin α4β1 expression and CNS migration, whereas pharmacologic inhibition of integrin α4β1 reduced the abnormal T cell presence in the CNS of β-catenin-expressing mice. Together, these results implicate deregulation of the Wnt/β-catenin pathway in CNS inflammation and suggest novel therapeutic strategies for neuroinflammatory disorders.

Original languageEnglish
Pages (from-to)3031-3041
Number of pages11
JournalJournal of Immunology
Volume199
Issue number9
DOIs
Publication statusPublished - Nov 1 2017

Keywords

  • Animals
  • Inflammation
  • Integrin alpha4beta1
  • Mice
  • Mice, Knockout
  • Spinal Cord
  • Spinal Cord Diseases
  • Th1 Cells
  • Wnt Signaling Pathway
  • beta Catenin
  • Journal Article
  • Research Support, Non-U.S. Gov't

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