Cyclin-dependent kinase 5 activity is required for T cell activation and induction of experimental autoimmune encephalomyelitis

• DOI: 10.1084/jem.20100876
• Publication Date: 2010-10-12T03:03:45Z
• Authors: Tej K. Pareek; Eric Lam; Xiaojing Zheng; David Askew; Ashok B. Kulkarni; Mark R. Chance; Alex Y. Huang; Kenneth R. Cooke; John J. Letterio
• Keywords: Cyclin-dependent kinase 5; Adoptive Cell Transfer

Cyclin-dependent kinase 5 (Cdk5) is a ubiquitously expressed serine/threonine kinase. However, requirement for Cdk5 has been demonstrated only in postmitotic neurons where there abundant expression of its activating partners p35 and/or p39. Although hyperactivation the Cdk5–p35 complex found variety inflammatory neurodegenerative disorders, potential contribution nonneuronal activity not explored this context. We describe previously unknown function T cells that required induction experimental autoimmune encephalomyelitis (EAE). cell receptor (TCR) stimulation leads to rapid lymphocyte activation. Chimeric mice lacking gene hematopoietic tissues (Cdk5−/−C) are resistant EAE, and adoptive transfer either Cdk5−/−C or p35−/− encephalitogenic lymphocytes fails disease. Moreover, our data reveal novel mechanism involving Cdk5-mediated phosphorylation actin modulator coronin 1a on threonine 418. Cdk5-deficient lack posttranslational modification exhibit defective TCR-induced polarization reduced migration toward CCL-19. These define distinct role biology suggest inhibition may be beneficial treatment cell–mediated disorders.