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The role of PIM kinases in human and mouse CD4+ T cell activation and inflammatory bowel disease.

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.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Jackson LJ,Pheneger JA,Pheneger TJ,Davis G,Wright AD,Robinson JE,Allen S,Munson MC,Carter LL

doi

10.1016/j.cellimm.2011.10.011

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

200-13

issue

2

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(11)00272-3

journal_volume

272

pub_type

杂志文章

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