Investigate the role of PKCλ/ι on Th17 cells and allergic airway inflammation

Abstract

Abstract We have reported that atypical protein kinase PKCλ/ι plays key roles for Th2 differentiation and cytokine secretion both in cell culture systems and in allergic airway inflammation. To determine the potential role of PKCλ/ι on Th17 cells, we did investigations both in vivo and in vitro with the use of conditional PKCλ/ι-deficient mice. We found that PKCλ/ι-deficient CD4+ T cells showed impaired ability to differentiate into Th17 cells in vitro under Th17-skewed culture conditions. This impairment for Th17 differentiation was associated with the down-regulation of Stat3 and IL-23R in PKCλ/ι-deficient CD4+ T cells in culture. The secretion of IL-17, IL-17F, IL21 and IL-22, Th17 effector cytokines, was reduced from PKCλ/ι-deficient T cells either under non-skewed or Th17-skewed conditions. Furthermore, allergic airway inflammations induced by ovalbumin (OVA) or house dust mite (HDM) were applied to study the role of PKCλ/ι-Th17 axis in vivo. PKCλ/ι-deficiency significantly inhibited airway inflammations as showed reduced infiltrating cells and Th17 effector cytokines in the lung and bronchoalveolar lavage (BAL) fluid. These findings suggest that PKCλ/ι might be one of novel regulators for Th17 cells. Future studies will focus on underlying molecular mechanisms how PKCλ/ι control Th17 cells.