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

First Author  Jackson LJ Year  2012
Journal  Cell Immunol Volume  272
Issue  2 Pages  200-13
PubMed ID  22078270 Mgi Jnum  J:181378
Mgi Id  MGI:5311102 Doi  10.1016/j.cellimm.2011.10.011
Citation  Jackson LJ, et al. (2012) The role of PIM kinases in human and mouse CD4+ T cell activation and inflammatory bowel disease. Cell Immunol 272(2):200-13
abstractText  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 naive 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, naive 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.
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