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

Authors :
Yang Y
Dong P
Zhao J
Zhou W
Zhou Y
Xu Y
Mei C
Guo F
Zheng Y
Yang JQ
Source :
Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2018 Mar; Vol. 1864 (3), pp. 934-941. Date of Electronic Publication: 2018 Jan 03.
Publication Year :
2018

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 (PKC) λ/ι is a new regulator for Th2 differentiation and function. However, the role of PKCλ/ι for Th17 cells remains elusive. In this study, we explored the effect of PKCλ/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 PKCλ/ι-deficient mice. Our findings indicate that PKCλ/ι regulates Th17 cells. The secretion of Th17 effector cytokines, including IL-17, IL-21 and IL-22, were inhibited from PKCλ/ι-deficient T cells under non-skewing or Th17-skewing culture conditions. Moreover, the impaired Th17 differentiation and function by the PKCλ/ι-deficiency 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. PKCλ/ι-deficiency significantly inhibited airway inflammations. The infiltrating cells in the lungs and bronchoalveolar lavage fluids were significantly reduced in conditional PKCλ/ι-deficient mice. Th17 effector cytokines were reduced in the bronchoalveolar lavage fluids and lungs at protein and mRNA levels. Thus, PKCλ/ι emerges as a critical regulator of Th17 differentiation and allergic airway hyperresponsiveness.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
0925-4439
Volume :
1864
Issue :
3
Database :
MEDLINE
Journal :
Biochimica et biophysica acta. Molecular basis of disease
Publication Type :
Academic Journal
Accession number :
29305916
Full Text :
https://doi.org/10.1016/j.bbadis.2018.01.001