PKC-θ is a drug target for prevention of T cell-mediated autoimmunity and allograft rejection

Abstract

Protein kinase C theta (PKC-θ) is a key kinase in mediating T cell receptor (TCR) signals. PKC-θ activated by T cell receptor (TCR) engagement translocates to immunological synapses and regulates the activation of transcriptional factors NFκB, AP-1, and NFAT. These transcription factors then activate target genes such as IL-2. T cells deficient in PKC-θ display defects in T cell activation, survival, activation-induced cell death, and the differentiation into inflammatory T cells, such as Th2 and Th17 cells both in vitro and in vivo. Since these effector T helper cells are responsible for mediating autoimmunity, selective inhibition of PKC-θ is considered a treatment for prevention of autoimmune diseases and allograft rejection.