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PKD, as a key enzyme for helper T cell generation 〜Novel drug target for autoimmune diseases〜

Release date: 2016.09.28

 

Research Results Medicine/Dentistry/Pharmaceutical Sciences

 Professor Yamasaki and Assistant professor Ishikawa found that protein kinase D (PKD) is crucial for helper T cell development under the collaborative research with Tokushima University, Osaka University and RIKEN.
 In this study, the research group has for the first time established “PKD-deficient mice” by depleting PKD2 and PKD3 in T cells (PKD2/3∆T mice). Strikingly, PKD2/3∆T mice fail to generate CD4+ single positive thymocytes, demonstrating that PKD is critical for helper T cell generation (Fig. 1).
The discovery of this novel and critical kinase for helper T cells underscore the importance of PKD as a promising therapeutic target for autoimmune diseases (Fig. 2). This research achievement has been published on September --, 2016, in the online edition of Nature Communications.
 For more information about this research, see “Protein kinase D regulates positive selection of CD4+ thymocytes through phosphorylation of SHP-1”, Ishikawa E., Kosako H., Yasuda T., Ohmuraya M., Araki K., Kurosaki T., Saito T., and Yamasaki S., Nature Communications, DOI:10.1038/ncomms12756

In the thymus of PKD-deficient mice, CD4-positive cells that are precursors of helper T cells are severely decreased (Red circle).

PKD is activated upon T cell receptor stimulation and phosphorylates SHP-1, which induces optimal TCR signaling leading to helper T cell development (left). On the other hand, inhibition of PKD may stop the supply of newly generated helper T cells. This could be a new strategy for the treatment of autoimmune diseases (right).

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