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SGK1 enhances Th9 cell differentiation and airway inflammation through NF-κB signaling pathway in asthma

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Abstract

This study aimed to explore the effect of Sgk1 on Th9 differentiation and the underlying mechanism in asthma. The asthmatic mouse model induced by ovalbumin (OVA) and CD4+T cells which were cultured with TGF-β, IL-2, IL-4, and anti-IFN-γ were applied in vivo and in vitro, respectively. Flow cytometry, quantitative real-time PCR (qRT-PCR), and ELISA were performed to detect T-helper 9 (Th9) cells, IL-9 expression, and IL-9 release. Western blot was performed to examine phosphorylated(p)-IKKα, p-IκBα, p-p65, and IRF4 levels. Hematoxylin/eosin (H&E) staining was adopted to assess pathological changes of lung tissues. Inhibition of Sgk1 dramatically reversed elevated Th9 cells and IL-9 expression in the lung tissues of asthmatic mice. In vitro, Sgk1 promoted Th9 differentiation and elevated p-IKKα, p-IκBα, p-p65, and IRF4 levels, but inhibition of IKKα/IκBα/p65 pathway and IRF4 both reversed enhanced Th9 differentiation by Sgk1. Sgk1→IKKα/IκBα/NF-κBp65→IRF4→Th9 axis may be implicated in asthma development.

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Author notes

  1. Xinqi Wu & Wei Jiang

    Present address: Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, No. 246 Xuefu Road, Nangang District, Harbin, 150001, Heilongjiang, China

Authors and Affiliations

  1. Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, No. 246 Xuefu Road, Nangang District, Harbin, 150001, Heilongjiang, China

    Chi Zhang, Jinlong Cai, Shuilian Yu, Jianhong Sun & Zhiliang Tian

  2. Department of Pneumology, Qingdao Women and Children’s Hospital, Qingdao, 266000, Shandong, China

    Xiaoli Wang

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  1. Xinqi Wu
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  3. Xiaoli Wang
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Correspondence to Jianhong Sun or Zhiliang Tian.

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Wu, X., Jiang, W., Wang, X. et al. SGK1 enhances Th9 cell differentiation and airway inflammation through NF-κB signaling pathway in asthma. Cell Tissue Res 382, 563–574 (2020). https://doi.org/10.1007/s00441-020-03252-3

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