Informace o publikaci

Wnt/beta-Catenin Signaling Induces Integrin alpha 4 beta 1 in T Cells and Promotes a Progressive Neuroinflammatory Disease in Mice

Autoři	SORCINI D. BRUSCOLI S. FRAMMARTINO T. CIMINO M. MAZZON E. GALUPPO M. BRAMANTI P. AL-BANCHAABOUCHI M. FARLEY D. ERMAKOVA O. BRITANOVA Olga IZRAELSON Mark CHUDAKOV Dmitriy BIAGIOLI M. SPORTOLETTI P. FLAMINI S. RASPA M. SCAVIZZI F. NERLOV C. MIGLIORATI G. RICCARDI C. BERESHCHENKO O.
Rok publikování	2017
Druh	Článek v odborném periodiku
Časopis / Zdroj	Journal of immunology
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	http://www.jimmunol.org/content/199/9/3031
Doi	http://dx.doi.org/10.4049/jimmunol.1700247
Klíčová slova	BETA-CATENIN; MULTIPLE-SCLEROSIS; WNT PATHWAY; THYMOCYTE DEVELOPMENT; GENE DOSAGE; STEM-CELLS; ACTIVATION; SURVIVAL; DIFFERENTIATION; EXPRESSION
Popis	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 alpha 4 beta 1, 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 alpha 4 beta 1 expression and CNS migration, whereas pharmacologic inhibition of integrin alpha 4 beta 1 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.