Atypical protein kinase PKCλ/ι on pathogenesis of asthma

Abstract

Abstract Asthma is a chronic airway inflammation in which Th2 and Th17 cells play critical roles in its pathogenesis. We have reported that atypical protein kinase PKCλ/ι is a new regulator for Th2 differentiation and function. Our recent findings indicate that PKCλ/ι may regulate Th17 cells. The secretion of Th17 effector cytokines, including IL-17, IL-17F, IL21 and IL-22, were inhibited from PKCλ/ι-deficient T cells under non-polarized or Th17-polarized culture conditions. Further studies indicate that impaired Th17 differentiation and function is associated with the down-regulation of Stat3, NFATc1 transcription factors in PKCλ/ι-deficient CD4+ T cells in culture. We developed a model of Th17 and neutrophil-involved allergic airway inflammation by intratracheal inoculation of allergenic extracts of house dust mite (HDM). PKCλ/ι-deficiency significantly inhibited airway inflammations. The infiltrating cells in the lungs and bronchoalveolar lavage (BAL) fluid were significantly reduced in conditional PKCλ/ι-deficient mice. Th17 effector cytokines were reduced in the BAL and lungs at protein and mRNA levels. Our findings suggest that PKCλ/ι might regulate allergic airway inflammation through the control of Th17 cells. The underlying molecular mechanisms are currently under investigation.