| First Author | Biswas PS | Year | 2011 |
| Journal | Cell Immunol | Volume | 266 |
| Issue | 2 | Pages | 111-5 |
| PubMed ID | 21111405 | Mgi Jnum | J:166968 |
| Mgi Id | MGI:4866933 | Doi | 10.1016/j.cellimm.2010.10.009 |
| Citation | Biswas PS, et al. (2011) Aberrant ROCK activation promotes the development of type I diabetes in NOD mice. Cell Immunol 266(2):111-5 |
| abstractText | Aberrant production of IL-21 by T cells is critical for the development of type 1 diabetes (T1D) in NOD mice. The pathogenic effects of IL-21 are partly due to its ability to promote the generation of T(H)-17 cells. Interferon Regulatory Factor (IRF4) is a crucial regulator of IL-17 and IL-21 production. We recently found that the serine-threonine kinase ROCK2 phosphorylates IRF4 and regulates its ability to control IL-17 and IL-21 production. Here we show that NOD T cells aberrantly activate ROCK2. We furthermore demonstrate that ROCK inhibition corrects the abnormal IRF4 function in NOD T cells and diminishes their production of IL-17 and IL-21. Importantly, administration of a ROCK inhibitor to NOD mice protects against diabetes development. These studies thus support the idea that ROCK2 is inappropriately activated in NOD T cells and that ROCK kinases could represent important therapeutic targets for the treatment of T1D. |
