Wnt/b-Catenin Signaling Induces Integrin a4b1 in T Cells and Promotes a Progressive Neuroinflammatory Disease in Mice.

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 b-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 ?-catenin expression in T cells leads to aberrant and Th1-biased T cell activation, enhanced expression of integrin a4b1, and infiltration of activated T cells into the spinal cord, without affecting regulatory T cell function. Importantly, expression of b-catenin in mature naive T cells was sufficient to drive integrin a4b1 expression and CNS migration, whereas pharmacologic inhibition of integrin a4b1 reduced the abnormal T cell presence in the CNS of b-catenin-expressing mice. Together, these results implicate deregulation of the Wnt/b-catenin pathway in CNS inflammation and suggest novel therapeutic strategies for neuroinflammatory disorders.