PKCλ/ι regulates Th17 differentiation and house dust mite-induced allergic airway inflammation.

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 λ/ι is a new regulator for Th2 differentiation and function. However, the role of for Th17 cells remains elusive. In this study, we explored the effect of duanyu1531λ/ι on Th17 cells in the context of ex vivo cell culture systems and an in vivo murine model of allergic airway inflammation with the use of activated T cell-specific conditional mice. Our findings indicate that duanyu1531λ/ι regulates Th17 cells. The secretion of Th17 effector cytokines, including IL-17, IL-21 and IL-22, were inhibited from duanyu1531λ/ι-deficient T cells under non-skewing or Th17-skewing culture conditions. Moreover, the impaired Th17 differentiation and function by the was associated with the downregulation of Stat3 and Rorγt, key Th17 transcription factors. We developed a model of Th17 and neutrophil-involved allergic airway inflammation by intratracheal inoculation of house dust mites. duanyu1531λ/ι-deficiency significantly inhibited airway inflammations. The infiltrating cells in the lungs and bronchoalveolar lavage fluids were significantly reduced in conditional duanyu1531λ/ι-deficient mice. Th17 effector cytokines were reduced in the bronchoalveolar lavage fluids and lungs at protein and mRNA levels. Thus, duanyu1531λ/ι emerges as a critical regulator of Th17 differentiation and allergic airway hyperresponsiveness.

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