Aberrant ROCK activation promotes the development of type I diabetes in NOD mice

作者：Biswas Partha S; Gupta Sanjay; Chang Emily; Bhagat Govind; Pernis Alessandra B^*

来源：Cellular Immunology, 2011, 266(2): 111-115.

DOI：10.1016/j.cellimm.2010.10.009

• Type 1 diabetes
• IL-21
• IL-17
• Signaling pathways

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.

• 出版日期2011