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Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):934-941. doi: 10.1016/j.bbadis.2018.01.001. Epub 2018 Jan 3.

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

Author information

1
Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control, Jiangsu Institute of Parasitic Diseases and Public Health Research Center of Jiangnan University, Wuxi, Jiangsu, China.
2
Model Animal Research Center, Nanjing University, Nanjing, Jiangsu, China.
3
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA.
4
Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control, Jiangsu Institute of Parasitic Diseases and Public Health Research Center of Jiangnan University, Wuxi, Jiangsu, China; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA. Electronic address: Junqi.Yang@cchmc.org.

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.

KEYWORDS:

Allergic airway inflammation; House dust mite; PKCλ/ι; Th17; Th2

PMID:
29305916
DOI:
10.1016/j.bbadis.2018.01.001
[Indexed for MEDLINE]

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