PKC- is a Drug Target for Prevention of T Cell-Mediated Autoimmunity and Allograft Rejection

Protein kinase C theta (PKC-) is a key kinase in mediating T cell receptor (TCR) signals. PKC- activated by T cell receptor (TCR) engagement translocates to immunological synapses and regulates the activation of transcriptional factors NF-κB, AP-1, and NFAT. These transcription factors then activate target genes such as IL-2. T cells deficient in PKC- display defects in T cell activation, survival, activation-induced cell death, and the differentiation into inflammatory T cells, both in vitro and in vivo. Since these effector T helper cells are responsible for mediating autoimmunity, selective inhibition of PKC- is considered a treatment for prevention of autoimmune diseases and allograft rejection.