The role of PIM kinases in human and mouse CD4+ T cell activation and inflammatory bowel disease.
Cell Immunol
; 272(2): 200-13, 2012.
Article
em En
| MEDLINE
| ID: mdl-22078270
ABSTRACT
PIM kinases are a family of three serine/threonine kinases expressed following T cell activation. Using potent selective small molecule antagonists of PIM-1/3 kinases, we demonstrate a potential role for these enzymes in naïve and effector CD4+ T cell activation. PIM-1/3 inhibition prevented CD4+ T cell proliferation by inducing a G0/G1 cell cycle arrest without affecting cellular survival. In the absence of PIM-1/3 kinase activity, naïve CD4+ T cells failed to fully differentiate into effector cells both in vitro and in vivo. Therapeutic dosing of a PIM-1/3 inhibitor was efficacious in a CD4+ T cell-mediated model of inflammatory bowel disease suggesting that PIM-1 and PIM-3 kinase activity contributes to sustained disease severity. These results demonstrate that PIM-1/3 kinases have an important role in CD4+ T cell responses and inhibition of this activity may provide a therapeutic benefit in T cell-mediated diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Inflamatórias Intestinais
/
Linfócitos T CD4-Positivos
/
Proteínas Proto-Oncogênicas c-pim-1
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Immunol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos