| First Author | Sorcini D | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 9 | Pages | 3031-3041 |
| PubMed ID | 28939758 | Mgi Jnum | J:254763 |
| Mgi Id | MGI:6103606 | Doi | 10.4049/jimmunol.1700247 |
| Citation | Sorcini D, et al. (2017) Wnt/beta-Catenin Signaling Induces Integrin alpha4beta1 in T Cells and Promotes a Progressive Neuroinflammatory Disease in Mice. J Immunol 199(9):3031-3041 |
| abstractText | 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 beta-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 beta-catenin expression in T cells leads to aberrant and Th1-biased T cell activation, enhanced expression of integrin alpha4beta1, and infiltration of activated T cells into the spinal cord, without affecting regulatory T cell function. Importantly, expression of beta-catenin in mature naive T cells was sufficient to drive integrin alpha4beta1 expression and CNS migration, whereas pharmacologic inhibition of integrin alpha4beta1 reduced the abnormal T cell presence in the CNS of beta-catenin-expressing mice. Together, these results implicate deregulation of the Wnt/beta-catenin pathway in CNS inflammation and suggest novel therapeutic strategies for neuroinflammatory disorders. |
