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Surfactant protein A modulates the activities of the JAK/STAT pathway in suppressing Th1 and Th17 polarization in murine OVA-induced allergic asthma

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Abstract

Asthma is an allergic inflammatory lung disease affecting nearly 300 million people worldwide. To better understand asthma, new regulators must be identified. We conducted a study to investigate the effect and mechanisms of action of surfactant protein A (SPA) in OVA-induced asthmatic mice. Treatment with SPA delayed the onset of asthma, decreased its severity, as well as notably suppressed pro-inflammatory cytokine production. Furthermore, SPA-treated mice possessed more leukocytes; more CD4+ T cells infiltrated the spleen in the SPA-treated mice than in the control mice, and there were decreased percentages of Th1 and Th17 cells in vivo. In addition, expression levels of the T-bet (Th1 transcription factor) and RORγt (Th17 transcription factor) genes were significantly downregulated by SPA treatment. Moreover, SPA reduced the production and mRNA expression of pro-inflammatory cytokine mRNAs in activated T cells in vivo. Mechanistically, SPA could inhibit STAT1/4 and STAT3 phosphorylation, resulting in the differentiation of Th1 and suppression of Th17 cells, respectively. In the presence of CD3/CD28 expression, STAT1/4 and STAT3 were activated but suppressed by SPA, which was responsible for the augmentation of Th1 and Th17 differentiation. This result showed that SPA can effectively modulate the JAK/STAT pathway by suppressing Th1 and Th17 differentiation, thus preventing asthma. The present study reveals the novel immunomodulatory activity of SPA and highlights the importance of further investigating the effects of SPA on asthma.

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Fig. 1: SPA protects against OVA-induced allergic asthma in mice.
Fig. 2: SPA reduces the production and mRNA expression of cytokines in activated T cells.
Fig. 3: SPA suppresses the polarization of Th1 and Th17 cells in vivo.
Fig. 4: The effect of the pan-STAT inhibitor SH-4-54 on SPA-treated allergic asthma mice.
Fig. 5: SPA suppresses Th1 differentiation in vitro by inhibiting STAT1.
Fig. 6: SPA suppresses Th17 differentiation in vitro by inhibiting STAT3.

Data availability

The data that support the present study are available from the corresponding author upon reasonable request.

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Funding

The work was supported by the Youth Program of Natural Science Foundation of China (No. 81900017), the Natural Science Foundation of China (Nos. 81770023 and 81770022), the Natural Science Foundation of Fujian Province (2019J01303), and the Joint Funds for the Innovation of Science and Technology, Fujian Province (2018Y9075).

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The study was conceived and designed by WG and XG. XC and RY conducted experiments. XC, RY, XL, WY, WG, and XG analyzed the data and interpreted the results. XC, RY, and XG wrote the paper. We confirm that all the listed authors have participated actively in the study, and have reviewed and approved the submitted paper.

Corresponding authors

Correspondence to Wen Gu or Xuejun Guo.

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The authors declare no competing interests.

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The experimental protocols were approved by the Ethics Committee of Fujian Medical University, and the study was conducted in accordance with the guidelines published in the NIH Guide for the Care and Use of Laboratory Animals.

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Chen, X., Yue, R., Li, X. et al. Surfactant protein A modulates the activities of the JAK/STAT pathway in suppressing Th1 and Th17 polarization in murine OVA-induced allergic asthma. Lab Invest (2021). https://doi.org/10.1038/s41374-021-00618-1

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