| First Author | Yang Y | Year | 2018 |
| Journal | Biochim Biophys Acta | Volume | 1864 |
| Issue | 3 | Pages | 934-941 |
| PubMed ID | 29305916 | Mgi Jnum | J:262164 |
| Mgi Id | MGI:6149318 | Doi | 10.1016/j.bbadis.2018.01.001 |
| Citation | Yang Y, et al. (2018) PKClambda/iota regulates Th17 differentiation and house dust mite-induced allergic airway inflammation. Biochim Biophys Acta 1864(3):934-941 |
| abstractText | 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 (PKC) lambda/iota is a new regulator for Th2 differentiation and function. However, the role of PKClambda/iota for Th17 cells remains elusive. In this study, we explored the effect of PKClambda/iota 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 PKClambda/iota-deficient mice. Our findings indicate that PKClambda/iota regulates Th17 cells. The secretion of Th17 effector cytokines, including IL-17, IL-21 and IL-22, were inhibited from PKClambda/iota-deficient T cells under non-skewing or Th17-skewing culture conditions. Moreover, the impaired Th17 differentiation and function by the PKClambda/iota-deficiency was associated with the downregulation of Stat3 and Rorgammat, key Th17 transcription factors. We developed a model of Th17 and neutrophil-involved allergic airway inflammation by intratracheal inoculation of house dust mites. PKClambda/iota-deficiency significantly inhibited airway inflammations. The infiltrating cells in the lungs and bronchoalveolar lavage fluids were significantly reduced in conditional PKClambda/iota-deficient mice. Th17 effector cytokines were reduced in the bronchoalveolar lavage fluids and lungs at protein and mRNA levels. Thus, PKClambda/iota emerges as a critical regulator of Th17 differentiation and allergic airway hyperresponsiveness. |
